Skin-transparency technique creates window of opportunity

A team of biomedical engineers from the University of Texas (UT) at Austin has developed a method to make tissue transparent for short periods of time—but long enough to improve certain laser procedures, they contend. Although the process has not yet been tested on human skin, the engineers say it could have broad implications for both diagnostic and therapeutic applications because it reduces photon scattering and enhances the ability to direct visible wavelengths of laser energy more deeply into tissue.

Using injections of glycerol and other hyperosmotic substances just under the skin's surface, the researchers have succeeded in making small areas of rat and hamster skin nearly transparent for 20 minutes or more. The glycerol was applied in vitro and in vivo to assess changes in tissue optical properties; initial results showed a 50% increase in transmittance and decrease in diffuse reflectance occurring within 5 to 10 minutes after the glycerol was applied. In addition, the reduction of the photon scattering increased the depth of visibility with optical coherence tomography (OCT) and enabled in vivo visualization of blood vessels.

"Scattering prevents us from seeing blood vessels near the surface of the skin because none of the light passes directly through the skin to reflect from the blood vessel back to our eyes," says A. J. Welch, professor of biomedical engineering at UT Austin and chief investigator of the project. "When we injected glycerol into the skin of a hamster, we could actually see a blood vessel that had not been visible" (see images).

The clearing occurs in vitro about five minutes after the glycerol is injected and reaches its optimum state at 20 minutes, according to Welch. When applied in vivo, the best transparency occurs within 10 minutes. In both cases, more glycerol can be added to extend the time of transparency. The depth of the clearing depends on how and where the glycerol is applied, Welch says. "With OCT, which can already see 1 mm into tissue, our technique enables you to see down to 4 or 5 mm," he says. "If just looking with the eye, you can see maybe a millimeter or so."

Applications

This may not sound like much, but it opens up a number of possibilities for applications such as retinal surgery and the targeting of tumors, both of which can be limited by the difficulty in controlling a laser beam as it passes through the skin's surface and other turbid media. However, light travels straight through transparent objects because they have similar or identical degrees of refraction throughout, according to Welch.

"We want to improve the diagnostics and see if you can focus the laser energy better into tissue," he says. "Say you want to target port-wine stains. What would happen if you could focus the laser energy more directly on the blood vessels?"

The key is the hyperosmotic agent, which drives out the water in tissue and has a high index of refraction. For example, glycerol can change the degree of scattering through small areas of tissue in two ways. When it is added to cells, the imbalance in pressure causes water to flow out from the cell. Glycerol enters at a slower rate. Over time, the process reverses and water begins to re-enter the cell. Researchers believe this shrinkage may bring certain tissue components, such as collagen fibers, closer together, modifying the way the photons scatter. In addition, glycerol changes the optical composition of tissue because the water that is replaced within the tissue has an index of refraction that matches tissue components such as collagen.

Glycerol may not prove to be the optimum agent, however, because it is alcohol-based. Welch and his colleagues are studying a number of hyperosmotic agents to determine which is most effective while being least toxic. Because the technique relies on index-matching to reduce scattering, it works best with short-wavelength and near-infrared lasers in the 400-nm to 1.3-µm range, according to Welch.

The skin transparency technique was first discovered by two graduate students, Eric Chan and Jennifer Barton, at the UT Austin College of Engineering. Chan is now employed by Indigo Medical (Cleveland, OH), while Barton is assistant professor of biomedical engineering at the University of Arizona. Doctoral candidate Gracie Vargas is continuing the research at UT Austin, and the university has applied for a patent on the process. Human-tissue studies are expected to be conducted by Masoud Mahtemadi's team in the laser laboratory at UT Medical Branch at Galveston.

Some companies have already expressed interest in working with the researchers to further develop and eventually commercialize the technique. One firm, BioTex (College Station, TX), which was founded by a group from Texas A&M University, has already received a Small Business Innovation Research grant to investigate the use of this process to enhance the removal of tattoos.