Wavefront shaping is used to reverse the optical distortion caused by Earth’s atmosphere and provide clear images of distant planets. Beyond astronomy, wavefront shaping in biomedicine is emerging as a promising tool for controlling and focusing light in complex scattering media. Researchers at Caltech led by professor Lihong Wang are translating the process to medical engineering, showing that medical wavefront shaping has the potential to provide sharply focused images of biological tissue to detect cancer below the skin, for example. The Caltech researchers used a photorefractive crystal to cancel out the distortion of light caused by the tissue. The photorefractive crystal acts as a mirror, maintaining the quality of the wavefront (that is, the shape of the lightwave passing through the tissue) by reversing the distortion it undergoes. The lightwave experiences the same distortion on the way to the mirror and on its return trip back, only in reverse, causing the distortion to cancel itself out. “When light goes through a scattered medium like a piece of tissue, it will simply scatter all over the place,” Wang said. “That means we can’t directly focus light deep in tissue.” The scattering has a cumulative effect, so the more scattering photons go through, the greater the distortion. The wavefront shaping technique for medical imaging addresses three key metrics: the shaping system’s speed, the control degrees of freedom, and the energy gain of the corrected wavefronts. The technique simultaneously achieves high speed, high control degrees of freedom, and high energy gain. The response time of the new technique is about 10 μs, with about 106 control modes, which corresponds to an average mode time of about 0.01 ns per mode. According to the researchers, this is more than 50× quicker than some of the fastest wavefront systems developed so far. Since biological tissue is alive and dynamic, the entire wavefront shaping process must take place in just 1 ms. “Only when you have the same object, in the same state, at the same location during the time reversal process can we cancel the wavefront distortion,” Wang said. Researchers in Caltech’s Andrew and Peggy Cherng Department of Medical Engineering have achieved a major step forward in medical imaging by taking inspiration from the field of astronomy. Courtesy of Caltech. Many small panels of mirrors compose the researcher’s mirror device. The multiple panels give the researchers more control over the tuning and shaping of the lightwaves — that is, more control degrees of freedom — enhancing their ability to cancel out distortion. The third key metric, and the one that was most challenging for the team to achieve, is the brightness, or reflectivity, of the mirror — that is, the energy gain. The multipaneled mirror used to realize high-speed wavefront shaping with high control degrees of freedom can also cause reflectivity to become too dim. To solve this issue, the researchers amplified the light. The researchers use a laser gain medium to amplify the scattered lightwaves reaching and reflecting off the mirror. The mirror remains the same, while the light moving to and from the mirror becomes amplified and brighter. “Metaphorically, this gain medium allows us to make the ‘magic mirror’ shinier. It polishes the mirror, so to speak,” Wang said. By combining photorefractive, crystal-based analog optical phase conjugation and stimulated emission light amplification, the researchers achieved an energy gain approaching unity — that is, more than three orders of magnitude larger than conventional analog optical phase conjugation. “We report this technique that simultaneously achieves high-speed, high-energy gain — that means high reflectivity — and high control degrees of freedom. That means all three metrics have been satisfied for the first time,” Wang said. “This is a major step forward.” The researchers anticipate that the newly described technique will help overcome the optical diffusion limit in photonics and translate wavefront shaping techniques to real-world applications. “Through the use of wavefront shaping, we can mitigate the scattering effect and focus deeper into biological tissue,” Wang said. The research was published in Nature Photonics (www.doi.org/10.1038/s41566-022-01142-4).