UNH Physicist Expands Vision of MRI with Gas

[David Gillum <David.Gillum@unh.edu>]

DURHAM, N.H. -- In the last 20 years, magnetic resonance imaging (MRI) has

opened a window on the human body, showing our inner workings in elegant

detail and earning the 2003 Nobel Prize in medicine for the chemists whose

research first revealed its potential, but there is one important area MRI

cannot see -- the lungs. 



A University of New Hampshire (UNH) physicist is beginning to correct MRI's

blind spot, however. Funded by $3.7 million in grants from the National

Institutes of Health, Bill Hersman, PhD, is altering a gas found in air to

expand the vision of MRI to the lungs.



With a $2.7 million, four-year grant from the National Heart Lung and Blood

Institute (NHLBI), Hersman, a professor of physics in UNH's College of

Engineering and Physical Sciences, will work with imaging experts from

Brigham and Women's Hospital in Boston to perfect new technology for

polarizing xenon gas. Used in MRI, polarized xenon promises to benefit

millions with chronic obstructive pulmonary disease, the fourth leading

cause of death in the United States. 



"Using xenon gas with magnetic resonance imaging could result in earlier

detection of lung problems," says Hersman. "There's a significant potential

for medical cost savings by extending the frontiers of noninvasive

diagnostics." 



MRI can't see into the lungs because it relies on the magnetic properties of

hydrogen atoms, found in most human tissue as the "H" in H2O. When exposed

to the powerful magnets of an MRI machine, the nuclei of hydrogen atoms

polarize, aligning with one end, or pole, of the magnetic field or the

other. When the magnet is turned off, the nuclei emit radio signals as they

return to their normal positions. American Paul Lauterbur won the 2003 Nobel

Prize for medicine for first demonstrating that two-dimensional images could

be produced by varying the strength of the magnetic field and analyzing the

radio signals produced. Briton Peter Mansfield shared the Nobel with

Lauterbur for showing how these signals could be rapidly analyzed, making

MRI practical. 



But lung tissues are filled with air. Without the millions of hydrogen atoms

found in other tissues, the lungs appear hazy in conventional MR images. By

filling the lungs with a gas that has been pre-polarized, scientists hope to

overcome this problem and offer an unprecedented view of the human lung. 



Research initially focused on polarized helium, but the kind of helium

needed is very expensive because it is not naturally occurring. Xenon, a gas

with anesthetic properties similar to nitrous oxide, is much cheaper. It

also has the added advantages of diffusing more slowly and dissolving into

lung tissue, both of which make it better at revealing damaged areas of the

lungs. But first the xenon must be polarized, and until now, scientists have

lacked the means of producing large quantities of highly polarized xenon.



A fundamental physics researcher, Hersman only learned of this applied

physics problem from another physicist he met socially. But Hersman was

familiar with gas polarizing techniques through his studies of the internal

structure of atomic nuclei, so he decided to tackle it. Well-funded

researchers from around the world were already working on this problem, but

Hersman and his team, starting with a 2-year grant of just $150,000, lead

the pack. "We have exceeded the capability of multimillion dollar efforts

elsewhere," says Hersman, "mainly because we had a spectacularly good idea

that really worked." 



Helium is polarized by mixing it with vaporized atoms of a metal called

rubidium in a glass cylinder and exposing the mixture to a polarized laser.

Like a clutch transferring power from a car's engine to its wheels, the

rubidium transfers polarization from the laser to the helium before cooling

and returning to its solid state. To increase the chances that the laser

will transfer its polarization to the rubidium atoms through random

collisions, the gaseous mixture is kept at high pressure so its atoms will

be densely packed into the cylinder. Other researchers have been trying to

adapt this process for xenon, but, faced with a shoestring budget, Hersman

brought a little Yankee ingenuity to bear. 



Hersman knew that at low pressure, rubidium would combine with xenon to form

short-lived molecules, transferring its polarization more efficiently in the

process. To take advantage of that, however, he would have to come up with a

better way to polarize the rubidium. His solution was amazingly simple.

Instead of pointing the laser in the same direction as the gas flow, he

turned it around and pointed it against the gas flow. He also made the glass

cylinder much longer to give the rubidium more time to be exposed to the

laser. 



"We just approached it with a new sheet of paper and started with flowing

things in opposite directions," explains Hersman. "It's a paradigm shift."



The polarization of rubidium is started as it enters by whatever laser light

reaches the bottom of the cylinder. As the gas rises up the cylinder at high

velocity, the rubidium becomes increasingly polarized the closer it gets to

the laser. By the time the mixture reaches the top of the cylinder, the

rubidium has combined with the xenon, transferred its polarization to it,

and cooled to the point where it is deposited on the cylinder walls, leaving

behind xenon that is 60-70 percent polarized. Hersman's technique produces

more highly polarized xenon than those of his competitors in Germany, Japan

and elsewhere in the United States. NIH's National Institute for Biomedical

Imaging and Bioengineering has awarded Hersman a separate, $1 million grant

to study the fundamental physics behind his approach.



During the first few years of the NHLBI grant, Hersman's team, which has

grown from one graduate student and a part time postdoctoral associate to

two graduate and four undergraduate researchers, will polarize xenon in his

UNH lab and transport it to Boston for use in trials at Brigham and Women's.

Kept well below its freezing point and in the presence of a strong magnetic

field, the xenon can remain polarized for nearly a day. In the last year of

the project, the researchers will build a xenon polarizer for the hospital.

Hersman envisions a day when regional centers will polarize xenon for use in

area hospitals, while a few larger hospitals may have their own polarizers.

He estimates that the apparatus for polarizing and storing the xenon will

cost a fraction of one MRI unit.



The NIH grants, both awarded in August, come in the nick of time, as Hersman

had been keeping the project going without external funding for several

months. He hopes to secure additional funding to investigate using xenon to

image blood flow. He says xenon could yield superior MR images of the

circulatory system that would aid in the study of cancer, Alzheimer's

disease and atherosclerosis.

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