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New Medical Imaging Technique Could Allow NMR/MRI to Trace Phenomena in Blood and Tissue

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By Lynn Yarris, [email protected]

December 16, 1996

BERKELEY, CA -- Observations of an anesthetic entering human red blood cells have been reported by researchers with the Ernest Orlando Lawrence Berkeley National Laboratory (Berkeley Lab). The observations were made using a technique designed to enhance the effectiveness of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI).

In the Proceedings of the National Academy of Sciences, the researchers reported that xenon gas, a common anesthetic, can be hit with a laser beam to polarize its atomic nuclei then directly introduced into blood or tissue to obtain high resolution time-resolved NMR/MRI images.

The research team included Alexander Pines, a chemist with Berkeley Lab and the University of California at Berkeley, Thomas Budinger, head of Berkeley Lab's Center for Functional Imaging, chemist Gil Navon, of Tel Aviv University, and Angelo Bifone, Yiqiao Song, Roberto Seydoux, Rebecca Taylor, Boyd Goodson, and Tanja Pietrass at Berkeley.

"We've shown that the local introduction of laser-polarized xenon solutions can be performed rapidly, concentrating the xenon at a target area," says Budinger. "It could be an alternative to radioactive isotopes in many (medical imaging) studies because polarized xenon improves MRI sensitivity to a factor that is close to the sensitivity of radiocarbon detection."

Previous research at Berkeley, Princeton University and other institutions has shown that the NMR/MRI signals from xenon gas can be greatly enhanced through "optical pumping," a process whereby polarization is transferred from laser light to atomic nuclei. Laser-polarized xenon, inhaled by subjects, has been used to obtain NMR/MRI images of the air spaces in lungs. However, once the xenon nuclei come in contact with red blood cells in the lungs, they lose their laser-enhanced polarization within several seconds, reducing their effectiveness for other tissues.

"One of the challenges for the use of laser-polarized xenon in medical applications has been to find a means of efficiently delivering xenon to the blood and tissues while maintaining the large polarization acquired during optical pumping," says Pines. The Berkeley Lab researchers achieved success by pre-dissolving laser-polarized xenon in a special "biologically compatible" solution. The polarized xenon gas was frozen at liquid nitrogen temperatures, sublimated, put into the special solution, then shaken until it dissolved. Following this treatment, loss of polarization during the injection procedure proved to be insignificant.

"Pre-dissolving our polarized xenon gas in a solution that can be directly injected into fresh blood or tissue, buys time and specificity," says Pines. "We were able to observe the xenon penetrating and exiting the red blood cells and to measure the kinetics."

According to the measurements, it takes about 20 milliseconds for a xenon atom to pass across the membrane of a red blood cell. The mechanisms of general anesthesia remains a mystery. Understanding how long it takes for an anesthetic such as xenon to access red blood cells is a step towards solving this mystery.

Results also indicate that laser-polarized xenon gas could be used to perform angiography as well as to image physiological phenomena in the blood system and in tissue specific to the heart, lungs, brain, and other organs.

The solutions into which the xenon was pre-dissolved included saline, Intralipid, and Fluosol. All are medically safe intravenous or oral media in which xenon can hold its polarized spin long enough to obtain NMR/MRI signals.

"Polarized xenon in these solutions as carriers has potential for imaging not only anatomic structures such as coronary arteries, but also for identifying molecular substrates peculiar to cancer," says Budinger. "The key to our work is the basic measurements of how xenon behaves in various lipid molecular assemblages that can be engineered to stay in the blood pool or seek (specific types of) cells or matrix proteins in the human body."

This research was funded by the U.S. Department of Energy through the Materials Science Division of the Office of Energy Research.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.

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