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Lung imaging: It's a gas

By Matt Kelly

Two University researchers have received $3.7 million in grants to continue their work in lung imaging.

James R. Brookeman, professor of radiology and biomedical engineering, and John P. Mugler III, associate professor of radiology and biomedical engineering, have been experimenting with techniques of examining lungs to detect such diseases as asthma, emphysema and cystic fibrosis. More than 350,000 Americans die each year from lung disease according to the American Lung Association, making it the nation’s third leading killer.

James Brookeman

Matt Kelly
Researcher James Brookeman (left) discusses the lung imaging process with lab tech specialists Jaime Mata and George Yu (right).

Working with their team of graduate students and clinical researchers, Brookeman and Mugler are using an in-vivo magnetic resonance imaging device with polarized noble gases originally developed by physicists at Princeton who were experimenting with the gases.

Most modern magnetic resonance imaging equipment needs water in the tissue to create a picture.

However, “there is little water in the lung, so you would just see a black hole,” Brookeman said of standard imaging techniques, which generates pictures of moisture in tissues. Using the polarized gas method produces images that are 10 to 100 times sharper than conventional methods. It provides a clear depiction of subtle lung ventilation defects not visible through other medical imaging technology, Brookeman said, therefore holding the potential for early detection of respiratory disease at a time where intervention is more likely to succeed.

The process was brought to the researchers six years ago by U.Va. doctor and Princeton alumnus Thomas Daniel. Dr. Robert M. Carey, dean of U.Va.’s Medical School, came up with the first $60,000 to purchase a gas polarizing machine.

The technique uses specially prepared helium 3 or xenon gases, cooked with a laser in a glass bulb for six hours, then mixed with nitrogen. Helium 3 is one of the smallest known gases and is considered “noble” because it does not mix with other gases. This low solubility makes it an ideal gas to use, since it does not move from the lungs into blood vessels or organs. Helium 3, however, is not naturally occurring and is derived from the decomposition of tridium, which is used in trigger devices for hydrogen bombs. Brookeman said while there is a limited supply of helium 3, xenon occurs commonly in the atmosphere.

Xenon, which dissolves into the blood, can be used to measure trans-membrane diffusion. Brookeman said that xenon at low doses can be a euphoric and an anesthetic in higher doses.

The patient breathes in the gas and researchers take an image of the lung, recording the sections of the lung into which the gas did and did not intrude, Brookeman explained.

“We can get a picture of the gas and study the lung from the inside,” Brookeman said. “We can see the areas where the gas is not going, which we call ventilation defect.”

Researchers believe the system will be very helpful in detecting emphysema, which effects 2 million people, and asthma, which effects 14 million.

The polarized gas technique cannot detect a tumor, Brookeman said, unless that tumor prevents air from entering part of the lung, but it may be able to detect the beginning stages of emphysema, giving doctors an early warning of the disease. He said there are some promising drugs available now that may be able to reverse emphysema that is discovered early.

In assessing asthma, Brookeman said researchers can use the images to determine the correct balance of medications. For cystic fibrosis, where mucous fills the lungs, he said the tests can show a section of the lung plugged by too much mucous.

Brookeman said the money would be used primarily to replace the lab’s old scanner.

“We’ve done 200 studies on it and it is eight years old,” he said. “We need a new machine with more advanced imaging capabilities.”

The team’s grant started July 2 and comes from divergent sources, with the state contributing $1.8 million from its Industry Inducement Program of the Commonwealth Technology Research Fund and the remainder primarily from Amersham Imaging Inc.

Princeton, where the technique was first devised, formed Magnetic Imaging Technologies Inc. in Durham, N.C., to exploit the technology. This firm was later bought by Amersham, which now has relationships with six research centers, including Princeton, the University of Wisconsin and research universities in Germany and England. Brookeman said U.Va. has done more than 200 trials, more than any other research facility.

The state is contributing money because there could be economic benefits for the research. Brookeman, in his application to the state, said that there would be increased employment in the testing operation, including hiring more people to work on the project, and he said the grant could leverage “substantial” federal grant monies for diagnostic imaging to the University. The growth of the center would also encourage Amersham and some pharmaceutical companies to invest in the center. He said there could also be opportunities for spin-off businesses.

Brookeman also makes the argument that since Virginia is a tobacco- producing state, the health impact of tobacco could be studied here.

Though the team’s imaging techniques were developed in Princeton, U.Va. researchers have been perfecting some techniques of their own. Brookeman said the University has several imaging-related patents pending, including a method of measuring how quickly the xenon dissolves into a subject’s system, as a way of determining the functionality of a lung.

More information about the center can be found on its Web site at http://imaging. med.virginia.edu/hyperpolarized/index.htm.


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