Images of structures inside the bodies of living patients obtained by nuclear magnetic resonance scanning have revolutionized medicine. But some parts of the body, such as the lungs, still cannot be visualized as clearly as physicians would like for assessing disease and planning treatments. That explains growing enthusiasm for a new type of magnetic resonance imaging (MRI) that can provide high-resolution scans of lungs and that shows potential for better imaging of the brain, colon and other organs.

Researchers at several centers in the U.S. and Europe have been exploring the technique. Volunteers inhale a lungful of an unusual isotope of either helium or xenon that has been "hyperpolarized." This means that a high proportion of the gas's atomic nuclei have their "spin"--a magnetic property of quantum particles--oriented in the same direction. Subjects then hold their breath for 10 seconds or so while they undergo an MRI scan in a specially tuned machine. Hyperpolarization makes the gas provide an MRI signal that is some 100,000 times stronger per nucleus than that produced by water, the substance normally visualized. The strong signal means internal spaces can be visualized at unprecedented resolution.

Researchers learned as long ago as 1960 that the nuclei of small quantities of helium 3 can be polarized with lasers. Later, others learned how to accomplish the same trick with xenon 129, the only other usable gaseous isotope. The hyperpolarized state can be maintained for hours, provided the gas is kept away from paramagnetic substances such as oxygen. The idea of using hyperpolarized gases in medicine is credited principally to William Happer and Gordon D. Cates, physicists at Princeton University, together with Mitchell Albert, now at Brigham and Women's Hospital in Boston. The technique is also proving useful in nonmedical research on foams and minerals.

Making hyperpolarized gases in the liter quantities necessary to image lungs was a challenge taken up in the 1990s by Magnetic Imaging Technologies, Inc., in Durham, N.C. MITI has developed a machine the size of a desk to do the job and has an exclusive license from Princeton and the State University of New York at Stony Brook to commercialize hyperpolarized gases for medical MRI. The company is collaborating with Nycomed Amersham near London, a large medical imaging concern that has international experience with licensing. Nycomed plans eventually to supply gases to imaging centers in their hyperpolarized state, says technology manager Tim Grey Morgan.

MITI's machine employs a laser to hyperpolarize rubidium atoms in a vapor--a relatively easy process. The rubidium atoms then transfer their spin to nuclei of helium or xenon mixed in with the vapor. Researchers at Johannes Gutenberg University in Mainz, Germany, use a direct, low-pressure technique that reaches higher levels of polarization than MITI's method can, but it works only for helium.

Most of the lung imaging done so far has used helium, which gives a stronger signal than xenon. In one study, 16 volunteers at the University of Virginia Health Sciences Center were scanned, and the technique showed the main divisions within the lungs as well as the spaces where major blood vessels run. The chronic obstructive pulmonary disease in three patients was plainly visible: the inhaled gas failed to reach large regions, which appeared on the scans as dark patches. Other scans also revealed some unrecognized lung defects and displayed a clear improvement in an emphysema patient who had parts of his lungs removed. "This is scary surgery," says Thomas M. Daniel, the surgeon who performed the so-called lung-shaving operation. "The trick is what part to take out." Daniel is confident the new technique will help him know what parts to extract in future operations.

Lungs are not the only organ that could benefit from better imaging. Daniel's physicist colleague James R. Brookeman has used helium 3 to visualize dogs' colons. Although the "helium enema" might be uncomfortable, Brookeman notes, it might be less so than the sigmoidoscopies that are now done routinely on humans to screen for colon cancer.

Progress toward optimizing image acquisition and other information from helium 3 MRI scans is rapid. At Johannes Gutenberg University, Hans-Ulrich Kauczor, Ernst W. Otten and their colleagues have developed special scanning techniques that can detect how quickly helium is diffusing in different parts of the lung, which could increase the ability to detect disease. And because oxygen makes hyperpolarized helium lose its spin faster, comparisons between scans made in rapid succession can reveal changes in regional oxygen concentration. That in turn should reveal the local blood flow, valuable information for doctors to know. Geneviève Tastevin of the CNRS Kastler Brossel Laboratory in Paris and others are studying how to use helium 3 to obtain high-quality images with machines using smaller magnets, which should bring down the cost and may offer technical advantages. G. Allan Johnson of Duke University has used highly hyperpolarized helium to visualize in animal lungs what he believes are acini, clusters of air-exchanging sacks only a few hundred microns across. "I am quite staggered at the speed with which the technology is developing," says Grey Morgan of Nycomed.

Helium 3 is not without problems, however. Governments extract the gas from expired tritium drained out of hydrogen bombs. Most helium 3 now comes from Russia, but the supply is limited, and the gas is expensive--several hundred dollars per liter. (It is abundant on the moon, deposited by the solar wind, but nobody is currently planning to go there to get it.) Xenon 129, in contrast, is abundant and cheap, and because it diffuses less rapidly it should ultimately yield sharper images, Johnson says. Moreover, it dissolves in blood, unlike helium, and despite its classification as an inert gas it interacts with biological chemicals, notes James R. MacFall of Duke.

When xenon 129 binds to chemicals in the body, its resonances are changed, points out physicist Ronald Walsworth of Harvard-Smithsonian Center for Astrophysics. That means researchers can tweak an MRI machine to visualize, or even depolarize, xenon in specific chemical environments, so that its movements and chemical associations can be tracked. Although hyperpolarized xenon is stable for only tens of seconds in the blood, that is enough time to image its transport to the brain and to distinguish white and gray matter there; xenon passes across the blood-brain barrier (producing anesthesia and euphoria). Even though xenon is harder to hyperpolarize and store than helium, Grey Morgan says Nycomed intends to bring xenon imaging up to the same level of sophistication as helium imaging. The result could be a remarkable new capability for medical science.

Since May of last year, most human work on hyperpolarized gases has been at a temporary halt. A court prompted the U.S. Food and Drug Administration to decide to regulate imaging agents as drugs rather than as devices. That means MITI has had to stop work on patients while it sponsors animal tests: several dozen beagles are now somewhere barking at a peculiarly high pitch as a result of being dosed with hyperpolarized helium 3. Bastiaan Driehuys, MITI's president, notes that divers breathe normal helium in large amounts and appear to suffer no ill effects--presumably because the gas does not dissolve in blood--but says the FDA is taking no chances with gases to be administered to patients with respiratory disease. One plausible concern is that rubidium could contaminate the product, so assays and materials have to be standardized.

Dreihuys says the FDA is expediting the process. He expects phase II clinical trials to start this year and is aiming for approval of helium 3 as a contrast agent in 2001. Better images will soon be in the air.

--Tim Beardsley in Charlottesville, Va.