Laser-light research targets diagnostic imaging

The Keck Foundation enables biomedical engineers to pursue a breakthrough diagnostic imaging technique.

What if a specially configured laser light could detect early-stage breast cancer or lung cancer? The W.M. Keck Foundation recently awarded Purdue biomedical researchers a $1 million grant to develop a new type of imaging technology for living cell and tissue analysis, which may lead to a disease-detecting diagnostic tool.

Central to the concept is a pioneering technique for in vivo spectroscopy, which uses a pulsing laser light to determine the precise chemical content of tissues in living organisms.

"The Keck Foundation grant provides vital funding to boost research into this innovative approach," says Purdue Provost Debasish "Deba" Dutta. "This Keck platform has the potential to resolve the complex machinery of a live cell, representing an advanced medical tool to improve human health."

If we know the chemical content of tissue, we can do early detection of disease with biomarker sensitivity, such as aggressive tumors or vulnerable plaques, which can rupture and cause a heart attack."

Professor, Weldon School of Biomedical Engineering and Department of Chemistry

The lead researcher is Ji-Xin Cheng, a professor of biomedical engineering and chemistry. Cheng also is principal investigator for the Molecular Spectroscopic Imaging Group in the Weldon School of Biomedical Engineering.

"This work is potentially very important," Cheng says. "If we know the chemical content of tissue, we can do early detection of disease with biomarker sensitivity, such as aggressive tumors or vulnerable plaques, which can rupture and cause a heart attack. This is not possible with current medical imaging technologies."

Currently, in vivo spectroscopy is impractical because when light interacts with molecules in living tissue, the photons scatter, making for inefficient detection of photon patterns.

"In 1666, Sir Isaac Newton used the word 'spectrum' to describe the rainbow of colors that are revealed when white light is passed through a prism," Cheng explains. "Unfortunately, this wisdom becomes highly inefficient when dealing with scattered photons from an intact organism. Our technique is designed to overcome this problem."

He is working with team leaders Andrew Weiner, the Scifres Family Distinguished Professor of Electrical and Computer Engineering; and Mingji Dai, an assistant professor in the Department of Chemistry.

"If perfected, in vivo spectroscopy could improve the practice of medicine dramatically, says George Wodicka, a professor and head of the Weldon School of Biomedical Engineering, and professor of electrical and computer engineering. "This generous grant from the Keck Foundation allows us to marshal an interdisciplinary team of top researchers to attack the considerable challenges associated with this work."

The new in vivo imaging approach hinges on a technique called frequency-multiplexed stimulated Raman scattering microscopy.

"This allows us to get a spectrum of individual molecules, revealing the chemical composition of the tissues," Cheng says. "Currently, we know the presence of target molecules, but we don't know where the molecules are, what their dynamics are, and how they interact with others inside the cell. This new platform may enable us to visualize how a cell executes its functions using fingerprint vibrations.

"Even though the scattering of light interacting with tissue changes the direction of photons, the frequency modulation of each color does not change," Cheng says. "This could allow us to code the laser light for detection of photons using a large detector placed near the specimen or organism being imaged."

The frequency modulation will be performed with an instrument invented by the Purdue researchers.

"A cell is not a bag of molecules," Cheng says. "It is akin to your body, with organs and specialized structures that perform a variety of functions. The challenge is to obtain a spectrum from highly scattered photons from tissue in vivo. Providing sufficient bandwidth at each pixel is a quantum leap because the information in a spectrum allows us to study inter- and intra-cellular interactions."

Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of Superior Oil Co. The Foundation's grant making is focused primarily on pioneering efforts in the areas of medical research, science and engineering, and undergraduate education.

"The Keck award will help us build a solid foundation, help us prove that our approach is practical and worth further study. Of course, our goal is to get this new technique out of the lab and into the hands of physicians and other health care professionals," Cheng says.

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