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DURHAM, N.C. -- Hawaiian crooner Don Ho's "tiny bubbles" is
meant to tug at the heart strings. Now, researchers at Duke
University Medical Center have created tiny bubbles of their
own to help them understand how the heart is hurting. They hope
the red-blood-cell-sized microbubbles filled with a special
type of helium gas will eventually allow doctors to make more
detailed measurements of blood flow in human organs, such as
the heart.

The study, published in the Sept. 1 issue of the Proceedings of the National Academy of
Sciences, shows it is feasible to suspend helium gas in the
microbubbles, inject it into the blood vessels of a mouse, and
take detailed magnetic resonance images (MRI) of the vessels.
The research was supported by the National Institutes of
Health, the National Center for Research Resources, the
National Science Foundation, and the Whitaker Foundation.

The researchers are using "hyperpolarized" helium gas as a
contrast agent to create high-resolution MRI images. They use
lasers to "excite" or hyperpolarize the helium's nucleus. The
hyperpolarized gas is inert to humans and animals, yet it
yields a strong MRI signal.

"We see this as an opportunity to get structure and function
information about blood flow and vessel health in a single MRI
scan," said G. Allan Johnson, director of Duke's Center for In
Vivo Microscopy and principal investigator of the study. "The
microbubbles provide a unique sensitive signal source, with no
background signal, which allows us to see blood vessels in
great detail."

Johnson said the technique combines the strengths of several
imaging technologies in one method. Like angiography or
conventional MRI, it could be valuable in vascular imaging, and
like positron emission tomography (PET) imaging, it could be
used in perfusion studies, which measure how much blood is
reaching tissue within an organ. Such studies are important in
assessing, for example, whether arteries partially blocked by
cholesterol plaques are dangerously reducing blood flow to the
heart or other organs.

Right now, doctors measure blood flow to the heart, brain or
other organs using PET, which uses radioactive tracers to
measure flow. Such studies are useful, but offer fairly low
resolution, as well as some exposure to radioactivity. In
addition, the tracer stays in the bloodstream for minutes to
hours and recirculates throughout the body every minute,
reducing the accuracy of measurements. By contrast, the
microbubble signal is "tapped" when the MRI magnet measures it,
and is destroyed. It does not recirculate, Johnson said.

Also, typical MRI scanners measure protons in water, which
is found almost everywhere in the body, meaning measurements
have significant background signals. Helium is not normally
found in the body, so the MRI picks up only signal, with no
background.

"This research could open up a new clinical resource -- one
in which vascular, perfusion and anatomical imaging can be done
all in one place, in a single non-invasive study," Johnson
said.

In 1995, a group of researchers in Duke's Center for In Vivo
Microscopy generated the first clear image of a human lung
using inhaled hyperpolarized helium gas. That technique is now
being tested in human clinical trials.

To extend that work, biomedical engineering graduate student
Mark Chawla, Johnson, and a team of physicists and
physiologists wanted to explore the use of hyperpolarized
helium gas imaging in other areas of the body. Unfortunately,
the gas doesn't dissolve well in blood, making it difficult to
introduce into the blood stream.

To solve the problem, Chawla adapted a technique sometimes
used by ultrasound radiologists. He created tiny microbubbles
of helium in a solution of commercially available ultrasound
contrast fluid. When he injected these microbubbles into
anesthetized mice and took MRI images of the animals, he was
able to create detailed images of the animals' arteries and
veins.

"We believe these microbubbles, since they are about the
size of a red blood cell, will be an accurate indicator of
actual blood flow, whereas current liquid contrast agents can
leak out of tiny blood vessels," Chawla said.

The microbubbles are different from larger air bubbles,
which can cause embolisms, or blockages, of arteries. The
microbubbles are very small -- from 2 to 30 microns. The red
blood cell is about 5 to 8 microns. The microbubbles circulate
along with blood cells throughout the bloodstream, ending up in
the lung, where the helium is exhaled and the microbubbles
dissipate.