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Harvard researchers devise a better way to look inside lungs

Despite huge advances in imaging of the human body over the last 30 years, the inner workings of the lungs have remained a mystery. The inability to obtain sharp images has stalled the development of drugs to treat chronic bronchitis and asthma and made it hard to diagnose emphysema and other lung diseases before they become debilitating.

Now, two competing Harvard University researchers think they're closing in on a solution.

By getting patients to breathe in a special form of xenon or helium gas while their lungs are scanned, the radiology professors have been able to use magnetic resonance imaging to capture unprecedented pictures deep inside the lungs' passageways. The images reveal precisely which parts of the lungs are getting oxygen, which are not, and precisely how much oxygen is reaching the bloodstream.

Patients are unlikely to get these scans any time soon. Conventional X-ray-based CT scans already provide high-quality images of the lung's structure and excel in detecting cancerous tumors.

But the new technique illuminates the workings of the lungs -- the ventilation and gas exchange that don't show up in conventional imaging -- suggesting strong potential for use in evaluation of drugs and early detection of diseases such as emphysema and pulmonary fibrosis.

"The lung's primary purpose is to exchange oxygen and carbon dioxide, but we can't see that with current imaging," said Dr. Warren B. Gefter, a radiologist at the University of Pennsylvania who has done similar research independent of the two Harvard researchers.

Traditional MRI works by placing the body in a magnetic field and detecting changes this causes in the water molecules that are spread throughout human tissue. Because lungs are filled with air, however, MRI cannot take good pictures of the lungs at work.

``You'd have to have the patient in there for a year" to get the same quality images you can get for other organs, said Samuel Patz , a researcher at Brigham and Women's Hospital, who is on the forefront of xenon imaging.

Mitchell S. Albert , also of Brigham and Women's, was the first to realize the medical potential of enhancing magnetic imaging with gases 15 years ago when he was a graduate student.

The gas first must be processed so that it will show up on an MRI scan, and after initial studies with xenon, Albert and others focused on helium, which was easier to work with and produces stronger magnetic signals .

Albert's helium imaging techniques can now pinpoint when and where constriction occurs in the lungs during an asthma attack -- the presence of helium in a particular location means oxygen can get there, too. Several pharmaceutical companies recently expressed interest in using the technique to test new drugs that would target the specific areas of constriction, Albert said.

But there isn't enough helium to go around for widespread diagnostic use in hospitals. The specific isotope of helium required for imaging is a byproduct of radioactive material used to make atomic bombs, and only a finite quantity exists.

To get around the limited supply, Patz, a former student of Albert's , is taking a second look at xenon imaging. With help from researcher William F. Hersman at the University of New Hampshire , Patz has been able to get increasingly sharper images from xenon when testing in healthy volunteers.

In the coming weeks, the two will begin the first tests of xenon imaging in patients with mild to moderate cases of lung diseases including emphysema, bronchitis, and asthma to see whether it clearly shows the effects on the lung. Hersman has founded a company to try to commercialize the xenon imaging technique.

In addition to their work with lung imaging, Patz and Albert are pursuing the use of xenon for brain imaging. Unlike helium, xenon is absorbed by body tissue when inhaled and travels to the brain via the blood. Xenon MRI could be used to depict blood flow in the brain better than conventional MRI, they say, and help identify areas of the brain affected by stroke and neurodegenerative diseases such as multiple sclerosis, Alzheimer's, and Parkinson's.

The only side effects of either gas are temporary changes in voice -- helium makes people talk in high tones, and xenon lowers the voice. Inhaled xenon can also act as a mild anesthetic, causing a high like that from breathing in laughing gas.

After years of research, Albert says, gas imaging techniques are finally starting to show promise.

``This is the only research I've been engaged in since I was a graduate student," said Albert, 44. ``I feel the technique is finally getting acceptance and coming of age."

(Correction: Because of a reporting error, a story about lung imaging in yesterday's Health/Science Section wrongly described the professional relationship between two Brigham and Women's Hospital researchers. Samuel Patz and Mitchell S. Albert are former collaborators.)

Click the play button below to hear scientists discuss using the gases helium and xenon to provide new ways to watch the lungs in action.

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