Ultrasound focuses light for greater penetration in fluorescence imaging of tumors.

Researchers at the California Institute of Technology in Pasadena have developed a technique that allows them to optically image tumors up to a depth of 2.5 mm inside biologic tissue.

Ultrasound focuses light for greater penetration in fluorescence imaging of tumors.

Optical imaging offers advantages over clinical imaging techniques such as positron emission tomography and magnetic resonance imaging; for instance, it allows researchers to detect the presence of specific molecules in a tumor with the use of fluorescent tags. But tissue more than a few micrometers thick scatters light, making it impossible to detect such molecules. Researchers at the California Institute of Technology in Pasadena have reported a technique that allowed them to optically image tumors up to a depth of 2.5 mm inside biologic tissue.

Changhuei Yang, PhD, a professor of electrical engineering and bioengineering and senior author on the study, previously reported a technique that makes it possible to see through biologic tissue by recording the way light scattered through the tissue and using that recording to send light back along its original path through the tissue, thus eliminating the blurring effect of scattering.

These diagrams illustrate the Caltech photoacoustic imaging technique. On the left, light enters the tissue sample and is scattered (shown in blue arrows). From above, ultrasound is focused into a small area inside the tissue. The ultrasound slightly shifts the frequency of any light that passes through that area, and that light (shown in green) is recorded. On the right, the recorded light is then sent back to retrace its steps to the small region where the ultrasound was focused, so the light itself is focused on that area. [Credit: Caltech/Ying Min Wang and Benjamin Judkewitz]
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These diagrams illustrate the Caltech photoacoustic imaging technique. On the left, light enters the tissue sample and is scattered (shown in blue arrows). From above, ultrasound is focused into a small area inside the tissue. The ultrasound slightly shifts the frequency of any light that passes through that area, and that light (shown in green) is recorded. On the right, the recorded light is then sent back to retrace its steps to the small region where the ultrasound was focused, so the light itself is focused on that area. [Credit: Caltech/Ying Min Wang and Benjamin Judkewitz]

These diagrams illustrate the Caltech photoacoustic imaging technique. On the left, light enters the tissue sample and is scattered (shown in blue arrows). From above, ultrasound is focused into a small area inside the tissue. The ultrasound slightly shifts the frequency of any light that passes through that area, and that light (shown in green) is recorded. On the right, the recorded light is then sent back to retrace its steps to the small region where the ultrasound was focused, so the light itself is focused on that area. [Credit: Caltech/Ying Min Wang and Benjamin Judkewitz]
View largeDownload slide

These diagrams illustrate the Caltech photoacoustic imaging technique. On the left, light enters the tissue sample and is scattered (shown in blue arrows). From above, ultrasound is focused into a small area inside the tissue. The ultrasound slightly shifts the frequency of any light that passes through that area, and that light (shown in green) is recorded. On the right, the recorded light is then sent back to retrace its steps to the small region where the ultrasound was focused, so the light itself is focused on that area. [Credit: Caltech/Ying Min Wang and Benjamin Judkewitz]

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To then focus this light on a specific area of tissue, Yang's group expanded on work led by biomedical engineer Lihong Wang at Washington University in St. Louis. When light encounters ultrasonic vibrations, the light's frequency shifts a little, changing it to a slightly different color. By focusing ultrasound waves on a specific area and recording only this color-shifted light, the Washington University group imaged only that area. Wang's group used this method to see 1 mm inside biologic tissue.

Using their playback technique, Yang and colleagues can send light back through the tissue with as much power as they want, giving them enough energy to see 2.5 mm inside tissue and to excite fluorophores or examine Raman interactions, Yang says. By combining this technique with the ultrasound focusing to scan an area of interest, the team created an image of tumor tissue embedded in 500 μm of polyacrylamide gel that was sandwiched between two 2.5-mm layers of chicken tissue.

Yang says that hardware improvements might let the approach reach a depth of 10 cm—the depth limit of ultrasound—perhaps within 5 years. He foresees doctors using the system to detect cancer early and, by using Raman spectroscopy to get very specific chemical information about tumors, reduce false positives in diagnosis. “The need for better diagnosis is a very strong one,” says Yang. “This technology can probably fill that niche nicely.”

Other potential applications include extending photodynamic therapies deeper inside tissues and even using the focused light as an optical blade to ligate blood vessels or ablate difficult-to-reach tumors without a surgical incision.

©2012 American Association for Cancer Research.
2012