Laser and Ultra Sound in Collaboration Laser and Ultra Sound in Collaboration
National Eye Institute

Harnessing the Power of Light and Sound to Examine the Eye

Fusing disparate technologies and expertise can help unlock doors to scientific breakthroughs. By combining light and sound, researchers from two NCRR-funded centers illuminated a new method to detect eye abnormalities.

Early diagnosis often is critical to treating medical issues; it certainly is true for vision-robbing conditions, including tumors of the eye, glaucoma and eye disorders due to diabetes. The researchers hope their new technique, which provides a nearly tenfold higher resolution than standard methods, will allow eye doctors to treat the precursors of disease before the eye has sustained permanent damage.

The idea for this approach came from Ronald H. Silverman of the Weill Cornell Medical College Ophthalmology Department. An expert on ultrasound imaging of the eye, Silverman had grown frustrated with the method’s limitations. Ultrasound can detect objects that are 0.015 cm across (about twice the width of a human hair), but the blood vessels and other attributes of the eye are often much smaller.

"I wondered if there might be some way that we could combine light and sound to get information that we couldn’t get with either technique by itself," Silverman said. He had heard about recent work in the field of photoacoustic imaging that used lasers and ultrasound detectors.

"It seemed like a great idea," he said. "There was only one small problem: I knew absolutely nothing about lasers."

In 2007, Weill Cornell received funding through NCRR’s Clinical and Translational Science Awards (CTSA) program, linking several partner organizations. So, Silverman looked for a collaborator nearby. He found Ying-Chih Chen, a physicist at the Center for the Study of Gene Structure and Function at Hunter College of the City University of New York, one of NCRR’s Research Centers in Minority Institutions (RCMI) and a partner with the Clinical and Translational Science Center (CTSC) at Weill Cornell.

Chen had both the equipment and the expertise Silverman needed. Moreover, he had been looking for real-world medical problems to work on, and Silverman had those in spades.

"It was great good luck that I found him," Silverman said.

Chen agreed: "Scientists usually work on what is familiar. This project allowed us to venture beyond our comfort zones to collaborate across disciplines."

Silverman and Chen received 18 months of pilot funding from the Weill Cornell CTSC. With these funds, they purchased materials and built a prototype eye scanner with a focused laser and high-frequency ultrasound. They reported on their technique in Applied Physics Letters in January 2009.

Then, the two applied for and won an American Recovery and Reinvestment Act administrative supplement award through the RCMI program to further develop the focused laser technique. Their work also has received support from the National Institute of Biomedical Imaging and Bioengineering, the Dyson Foundation and the Riverside Research Institute.

"This research is a perfect example of breaking down walls between institutions and creating collaborations that would never exist without the CTSA," said Julianne Imperato-McGinley, the director and principal investigator of the Weill Cornell CTSC.

Robert Dottin, director of the gene center at Hunter College, agreed. "It is a great credit to NCRR for promoting collaborations among its grantees," he said.

Ying-Chih Chen of the Center for the Study of Gene Structure and Function at Hunter College examines a prototype eye scanner with a focused laser and high-frequency ultrasound. The brainchild of Chen and Ronald H. Silverman of Weill Cornell Medical College, the scanner uses photoacoustic imaging to study the eye and can take picture of objects just 0.002 cm across, about the size of an eye capillary. Photo by Y.C. Chen.

The collaboration far exceeded any goals Chen or Silverman could have hoped to achieve individually. By combining their expertise, they succeeded in developing new methods for examining the eye.

Sound and Light Unite

The new technique uses photoacoustic imaging, in which short light pulses from a laser cause a small but rapid expansion of tissue. The tissue expansion generates ultrasound waves, which can be detected and turned into images. This process is not new, but Silverman and Chen sought to reduce the noise and improve the resolution of the resulting images. To do this, they used focused lasers, which can target much smaller areas of tissue than can ultrasound alone.

The result was impressive. Their technique could provide images of objects just 0.002 cm across, about the size of a capillary in the eye.

Photoacoustic imaging also has several characteristics that should make it clinically useful, according to Silverman and Chen. It allows a greater distance between the ultrasound detector and the parts of the eye being studied—an essential step for noninvasively examining features in the back of the eye. Because the back of the eye is about an inch behind the cornea, ultrasound alone cannot provide images of it at the required resolution, but this new technique can.

Not only are photoacoustic images high resolution, they also provide novel information. Ultrasound images are limited to showing changes in tissue density, which can indicate an abnormality. But photoacoustic images can show pigments, which can provide critical clues about the health of the eye.

Pigments in the eye include melanin, which occurs in abnormal tissues, such as tumors, as well as in normal features, such as the iris and retina. Another important pigment in the eye is hemoglobin, which appears red when oxygenated and blue when deoxygenated. Deoxygenated tissue may not be getting enough oxygen or may be diseased.

Silverman and Chen are working to develop a "tunable" laser that can vary the wavelengths of light it emits depending on the pigment scientists hope to analyze. By adjusting the wavelength of the light emitted by the laser, Silverman and Chen hope to map the distribution of specific molecules within a tissue, which could be useful in identifying conditions such as glaucoma or tumors.

Yinh-Chi Chen (left) of Hunter College and Ronald H. Silverman of Weill Cornell Medical College perform a photoacoustic imaging study of nanoparticles suspended within the eye. Such particles offer a means of tracking flow and possibly targeting therapy of diseases, including glaucoma, mascular degeneration and ocular tumors. Photo by Fanting Kong.

"We’d like to have a tool that would give us new information that would be of diagnostic significance," Silverman said.

Silverman and Chen also want to try adding a staining material called a tracer. They are working with nanotechnologists at the Hunter College gene center to use gold nanoparticles as tracers in the eye’s transparent fluids. By injecting the tracers into the eye, the scientists hope they will be able to use their photoacoustic technique to observe fluid flow—a critical element of glaucoma—and to detect whether drugs change the flow.

"The contribution being made by Hunter College’s nanotechnologists will be critical to the success of the photoacoustic technique," said Sidney A. McNairy, director of NCRR’s Division of Research Infrastructure. "Thanks to the RCMI program, we can connect the know-how from two schools of knowledge that ultimately could have a significant impact on patient outcomes."

Challenges remain, including ensuring that the laser meets Food and Drug Administration safety guidelines. The team also needs to determine the best way to use the scanner with patients because the scanner requires a fluid to carry ultrasound waves to the detector. Possibilities include placing the detector directly against the eye or eyelid or immersing the eye in fluid.

"The developers of this imaging technique did just what we intended the CTSA program to accomplish: bring scientists together to accelerate clinically important research," said Anthony R. Hayward, director of NCRR’s Division for Clinical Research Resources.

"With this technology, we should be able to detect eye disease much earlier and with greater accuracy, thereby improving outcomes," Silverman added. Moreover, the technological advance may prove useful in examining other parts of the body and diagnosing other diseases. He and Chen envision eventually offering this imaging technology to medical centers to perhaps become a routine screening instrument for disease prevention and detection.