News from
PRINCETON UNIVERSITY
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Princeton, New Jersey 08544-5264
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Release: April 21, 1995
Contact: Jacquelyn Savani (609/258-5729)
Researchers Discover New Way
To Do MRI That Produces the
Best Ever Pictures of Lungs
Princeton, N.J.--A team of researchers led by Princeton University
physicists William Happer and Gordon Cates and Stony Brook
University chemist Arnold Wishnia has discovered a new way to do
Magnetic Resonance Imaging (MRI) with laser-polarized xenon gas
that enables, for the first time, really good pictures of lungs.
The Princeton physicists are also collaborating with researchers
at Duke University led by G. Alan Johnson to extend this new
technology to the use of laser-polarized helium gas.
Physicians need good pictures for accurate diagnosis--the better
the picture, the more likely the diagnosis will be right. While
further research is certainly needed to establish unambiguously
what is feasible, many exciting possibilities exist for the use of
this new technique in medicine. Take, for instance, the case of a
suspected pulmonary embolism, a blood clot in the lungs that can
dislodge into the heart and kill the patient; the treatment is to
eliminate the clot before it moves. Happer and Cates's discovery
should enable physicians to detect pulmonary embolisms much better
than they can with the best existing technology such as
ventilation perfusion scans.
The new technique promises to provide physicians for the first
time the capability to map lung functioning. Determining what
part of the lungs is functioning and what part not is particularly
helpful for treating conditions such as emphysema.
Other especially promising applications include imaging the blood
in vessels of the heart, which is important for diagnosing various
heart conditions. So the new technique may provide an alternative
or supplement to the current technique of angiography, which uses
x-rays to image iodine injected into the patient's blood.
Another possible use of the Happer-Cates discovery is for imaging
brain function by tracing how various stimuli affect the flow of
blood in the brain.
They call their technique "hyperpolarized gas imaging." To put it
into use does not require manufacturing a costly new type of MRI
machine. Rather, existing machines (of which there are some 3,000
in the United States and 6,000 worldwide) can be retrofitted to
incorporate the capability of imaging hyperpolarized gas.
Conventional MRI works by polarizing the protons in the water of a
patient's body. Protons along with neutrons are the fundamental
particles that make up the nuclei of atoms. The human body is
made mostly of water, which consists of two hydrogen atoms and one
oxygen atom. The hydrogen atoms have one proton in the nucleus so
that the body has a myriad of atoms consisting of one proton.
Protons like other fundamental particles have a property called
spin or angular momentum. That spin has associated with it what
physicists call a magnetic moment, so that each spinning proton is
like a little magnet with north and south poles. A key idea
behind MRI is to line up the spinning protons in the hydrogen
atoms so that the north poles are pointing the same direction and
the magnetic moments of individual protons come together to create
a big magnetic field. That alignment is called polarization.
With conventional MRI the protons are polarized by putting the
patient in a strong magnetic field. Then a pulse of radio waves
tips the aligned proton-spins so that they are perpendicular to
the strong magnetic field supplied by the machine. The tipped
proton-spins precess around like a top wobbling about its axis of
rotation. That precessing--in effect, a rotating magnetic moment-
-causes the signal which provides images of the body's interior.
Instead of polarizing the protons in the patient's body, Happer
and Cates's technique polarizes gases ("noble" or inert gases such
as xenon or helium). The patient will inhale the polarized gas
which can then be detected in the airways of the lungs and
dissolved in blood flowing to the nearby heart and brain.
Conventional MRI yields, by contrast, very poor images of the
lungs because, among other reasons, they are filled with air and
contain little water.
Happer and Cates use lasers to produce very high polarizations in
the nuclei of noble gases. They easily achieve polarizations
100,000 times more than the polarizations of the body's hydrogen
protons in an MRI machine.
The two keys to producing hyperpolarized gases are optical pumping
and spin exchange. Happer is one of the world's experts on these
phenomena.
Optical pumping is a technique whereby one uses lasers to produce
very high polarization in, particularly, alkali-metal atoms, such
as rubidium, cesium, potassium, and sodium. Alkali-metal noble
gas spin exchange (first accomplished at Princeton in the 1960s)
allows one to take the polarization from the alkali-metal atoms
and transfer it to noble gas atoms.
"Slowly but surely," says Cates, "through these spin exchange
collisions, the angular momentum of the alkali-metal atoms is
transferred to the nuclei of the noble gas atoms. Now, that may
sound simple, but you have to understand many details of the
physics of what is going on if you expect this to work."
Happer has been working on understanding those details of atomic
physics for 25 years. By 1972 when he wrote a heralded review
article entitled simply "Optical Pumping" for Reviews of Modern
Physics, Happer was a master of this subject. In the late 1970s
he became very interested in spin exchange and started doing
experiments to understand it better. By the early 1980s he had
succeeded in polarizing high pressure gases simultaneously with
achieving high polarizations.
This new hyperpolarized-gas technique for imaging especially lungs
is a byproduct of Happer's years of research into the basic
science of optical pumping and spin exchange. What motivated
Happer's research? "Curiosity," he says, "before the last few
years when we began to envision this application, it was all done
out of sheer curiosity and interest." He commends the Air Force
Office of Scientific Research (AFOSR) for its decades of support
for the basic science research that has led to hyperpolarized gas
imaging. "They showed commendable understanding of how
technological advances occur," says Happer. In addition to AFOSR,
Happer and Cates's work on imaging has been supported by grants
from the Advanced Research Project Administration (ARPA).
Cates came to Princeton in 1987 to work with Happer. Shortly
thereafter they got the idea that imaging with noble gases could
be an exciting possibility. They explored the idea for several
years and convinced themselves it was possible, and so mentioned
the possibility in passing in an article they submitted for
publication in 1992 and published in 1993. What stalled their
progress was the lack at Princeton of the kind of clinical testing
facility that medical schools have.
In the fall of 1992 Happer (then director of the DOE Office of
Energy Research) visited the State University of New York at Stony
Brook and talked with Wishnia, who had told Happer that he and a
graduate student, Mitchell Albert, had independently come up with
the idea of imaging with hyperpolarized gases. They had the same
idea but knew little about hyperpolarizing gases. So Cates
arranged to take the hyperpolarized gas to Stony Brook, which had
the equipment to image the gas.
That experiment on Feb. 11, 1993, worked; the researchers obtained
the first polarized noble gas image ever made. By July of 1993
the researchers produced the first images of a mouse's lungs.
Their demonstration of the feasibility of the new technique
appeared in an article, "Biological Magnetic Resonance Imaging
Using Laser-Polarized 129Xe," published in =Nature= in July of
1994.
The patent on the invention has been filed jointly by Princeton
and Stony Brook. In addition to Happer, Cates, and their SUNY
collaborators, the names of two Princeton graduate students in
physics will appear on the patent, Bastiaan Driehuys and Brian
Saam.
The collaboration with Stony Brook has focused on the use of
hyperpolarized xenon for imaging. Happer and Cates have also
entered into a collaboration with researchers associated with Duke
University and its Center for In Vivo Microscopy, directed by
Johnson. The work with the Duke collaborators currently focuses
on the use of hyperpolarized helium (3He).
Happer, Cates, Johnson, Robert Black (also at Duke), and Robert
Lontz (a North Carolina consultant) are organizing a start-up
company located in the research triangle near Duke. Their
product, says Cates, will make large quantities of polarized gas.
"The picture to have in mind," he says, "is of a desk-size unit
that is reasonably user friendly with a mask that you put on the
patient and use with an existing MRI machine with relatively few
retrofits."
As with Happer, it was Cates's interest in basic science that led
to the practical application. "One of the reasons," he says,
"that it's straightforward for us to scale this up and do this
imaging work is that for some years I and others have been
interested in using polarized noble gases as polarized nuclear
targets for particle physics experiments."
Happer was invited to give a talk, "Spin Exchange Optical Pumping
of Rare Gases and Hydrogen," on April 21 at the American Physical
Society's annual Washington, D.C. meeting. The talk includes a
description of the new imaging technology.
Note: For photographs call the Communications Office at Princeton
University (609) 258-3601.