In the caltech experiment, green laser light is combined with ultrasound and shone through a tissue sample, pictured in the center. Engineers at the California Institute of Technology have developed a new imaging technique that may lead to advances in solid-tissue imaging and in cancer treatment in the not-so-distant future. Details of the technique, which allows scientists to “see” into solid tissue through the use of light beams and ultrasound, were published June 26 in the journal Nature Communications.

Fluorescence imaging serves as one of the most important research tools in biomedical science, allowing clinicians, for example, to target tumors with fluorescent dyes and "see" them without cutting into the body. However, it’s difficult to image thick biological samples – those beyond approximately one millimeter – using fluorescence imaging because the light scatters.

Still, even when the light scatters, it contains important information about the sample, and researchers can determine ways to use that information. In previous research, Caltech professor of electrical engineering and bioengineering Changhuei Yang and his colleagues were able to record all the information about how light beams projected through tissue samples scattered, and then play that recording back in reverse to, in effect, retrace the light’s path to the original source and produce an image of that source.

“These methods are, in many ways, analogous to adaptive optics methods used in astronomy to cancel out the effect of atmospheric scattering,” the researchers wrote in their paper. “However, in contrast to astronomy, where it is sufficient to image through a turbid medium (the atmosphere), the goal of biomedical imaging is to image inside.”

In this most recent research, the team was able to extend the reach of the light to approximately two and a half millimeters. In theory, the technique eventually could enable scientists to focus light as deep as a few inches into tissue, which could lead to a less invasive way of diagnosing and treating diseases like cancer.

The work builds on a previous technique that scientists at Washington University in St. Louis developed to focus light using the high-frequency vibrations of ultrasound. Ultrasound has two useful properties: first, its sound waves are not scattered by tissue (which is why it works well to show images of fetuses in utero), and second, its vibrations interact with light in a predictable way to shift the light’s frequency slightly but perceptibly. Light that has interacted with ultrasound appears as a slightly different color.

In both the Caltech and Washington University in St. Louis experiments, the researchers focused ultrasound waves into a small region inside a sample of tissue, and then shone light on the sample. The Washington University experiment was limited because it only enabled the researchers to use a very small amount of light, but the Caltech experiment built on that to allow use of a much more powerful beam of light.

The Caltech team also demonstrated how its new method could be used with fluorescence imaging, which is a technique used in a variety of biological and biomedical research. The researchers showed that their technique allowed them to take images of tumors flagged with fluorescent dyes.

In a show of school spirit, they also embedded a patch of gel with a fluorescent pattern that spelled out “CIT” inside a tissue sample, and then scanned the sample with focused light beams. The focused light hit and excited the fluorescent pattern, resulting in the glowing letters “CIT” appearing from inside the tissue.

Once the technique is improved, it could reach a depth of 10 centimeters, or almost four inches. Researchers first shone light through a sample and recorded the path information of the light that interacted with the ultrasound. They then shone light back through the sample along that same path, resulting in focused light in one region of the sample. Then, it could be used for “a wide range of in vivo applications, including molecular imaging, early cancer diagnosis, photodynamic therapy and targeted excitation of optogenetic tools in deep tissues,” the researchers concluded in their study.

The technique could allow doctors to target light-sensitive chemotherapy drugs into tumors farther beneath the skin’s surface, and diagnose cancer earlier and more easily via imaging, as opposed to surgery.

Source:

Y.M. Wang et al. Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light. Nature Communications. Published online 26 June 2012. doi:10.1038/ncomms1925.