Ying Ming Wang Ties Light to Sound for Surgical Uses

Caltech bioengineering grad student Ying Ming Wang has succeeded in using deep penetrating ultrasound as a guide so laser light can be focused below the surface of tissue for imaging and even incision-less surgery.

The technique developed by Wang and colleagues overcomes the one-milimeter limit for focusing light inside tissue to reach two and a half millimeters. More importantly, the technique opens the door to refinements that may allow surgeons to focus powerful laser beams up to four inches into tissue — the depth limit of ultrasound itself.

“It enables the possibilities of doing incision-less surgery,” says Changhuei Yang, the Caltech professor of electrical engineering and bioengineering who served as senior author on Wang’s study. “By generating a tight laser-focus spot deep in tissue, we can potentially use that as a laser scalpel that leaves the skin unharmed.”

A technique Yang and colleagues had pioneered earlier served as the starting point for the breakthrough by Wang and Caltech postgraduate researcher Benjamin Judkewitz . Yang had devised the concept of shining light through tissue while recorded the resulting light scatter on a holographic plate. By playing the recording in reverse, Yang’s team could retrace the original path of the light back to its source. The retracing technique allowed them to offset the scattering of light as it penetrated layers of tissue, eliminating the blurring.

Wang’s goal was to expand the technique to get images of cells or molecules embedded deep within tissue.

“For biologists, it’s most important to know what’s happening inside the tissue,” Wang explains.

Wang and Judkewitz combined Yang’s work with that of Lihong Wang at Washington University in St. Louis (WUSTL). WUSTL’s Wang had combined ultrasound’s property of being able to penetrate tissue without scattering with the ability of ultrasound vibrations to slightly shift the frequency of light with which it interacts.

Caltech’s Wang focused ultrasound waves into a small region inside a tissue sample. then shone light into the sample. Due to the acousto-optic effect explored by WUSTL’s Wang, the portion of the scattered light that passed through the region with the focused ultrasound changed to a slightly different color, allowing Wang to pick out and record the color-shifted light. He then used the holographic playback technique devised by his Caltech mentor to retrace the path of just the color-shifted light from the focal area of the ultrasound. That allowed a focused image to be created from the ultrasound-shifted light.

Wang was able to achieve a big advance over the WUSTL work by being able to use the retracing technique to use a beam of light with as much power as they want, opening the door to other applications like incisionless surgery.

One application of the new Caltech process might be to treat cancer with photodynamic therapy in which a drug that contains light-sensitive, cancer-killing compounds is injected into a patient. The compounds are absorbed preferentially by cancer cells. When light shines on the cells, the compound is activated, killing the cells. Currently such photodynamic therapy is only used on the surface of tissue because of the scattering of light. Wang’s new technique would allow doctors to reach cancer cells deeper inside tissue.

Future improvements on the optoelectronic hardware used to record and play back light should allow penetration of focused light to 10 centimeters (almost 4 inches) within a few years, Wang says.

“It’s a very new way to image into tissue, which could lead to a lot of promising applications,” says Caltech’s Wang.

Their study paper, entitled “Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light” was published in the June 26 issue of Nature Communications.

The work was supported by the National Institutes of Health, the Defense Advanced Research Projects Agency (DARPA), the Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust, and Singapore’s National Science Scholarship from the Agency for Science, Technology and Research.

Ying Min Wang is currently a PhD candidate in biophotonics in Caltech’s bioengineering department. She received her BSE in biomedical engineering at Duke University in May of 2006.