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The 30-nanometer particle consists of a magnetic core and a thin gold shell, analogous to an eggshell, that surrounds but does not touch the center. Credit: Xiaohu Gao, University of Washington
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Spotting
a single cancerous cell that has broken free from a tumor and is
traveling through the bloodstream to colonize a new organ might seem
like finding a needle in a haystack. But a new imaging technique from
the University of Washington is a first step toward making this
possible.
UW
researchers have developed a multifunctional nanoparticle that
eliminates the background noise, enabling a more precise form of medical
imaging – essentially erasing the haystack, so the needle shines
through. A successful demonstration with photoacoustic imaging was
reported today (July 27) in the journal Nature Communications.
Nanoparticles
are promising contrast agents for ultrasensitive medical imaging. But
in all techniques that do not use radioactive tracers, the surrounding
tissues tend to overwhelm weak signals, preventing researchers from
detecting just one or a few cells.
"Although
the tissues are not nearly as effective at generating a signal as the
contrast agent, the quantity of the tissue is much greater than the
quantity of the contrast agent and so the background signal is very
high," said lead author Xiaohu Gao, a UW assistant professor of
bioengineering.
The
newly presented nanoparticle solves this problem by for the first time
combining two properties to create an image that is different from what
any existing technique could have produced.
The
new particle combines magnetic properties and photoacoustic imaging to
erase the background noise. Researchers used a pulsing magnetic field to
shake the nanoparticles by their magnetic cores. Then they took a
photoacoustic image and used image processing techniques to remove
everything except the vibrating pixels.
Gao
compares the new technique to "Tourist Remover" photo editing software
that allows a photographer to delete other people by combining several
photos of the same scene and keeping only the parts of the image that
aren't moving.
"We are using a very similar strategy," Gao said. "Instead of keeping the stationary parts, we only keep the moving part.
"We
use an external magnetic field to shake the particles," he explained.
"Then there's only one type of particle that will shake at the frequency
of our magnetic field, which is our own particle."
Experiments
with synthetic tissue showed the technique can almost completely
suppress a strong background signal. Future work will try to duplicate
the results in lab animals, Gao said.
The
30-nanometer particle consists of an iron-oxide magnetic core with a
thin gold shell that surrounds but does not touch the center. The gold
shell is used to absorb infrared light, and could also be used for
optical imaging, delivering heat therapy, or attaching a biomolecule
that would grab on to specific cells.
Earlier
work by Gao's group combined functions in a single nanoparticle,
something that is difficult because of the small size.
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On top are photoacoustic images taken for gold nanorods (left), the new UW particle that has a magnetic core and surrounding gold shell (center), and a simple magnetic nanoparticle (right). Below is the same image after processing to remove pixels not vibrating with the magnetic field. The center blob is retained because of the particles' magnetic core and is bright because of the particles' gold shell. Credit: Xiaohu Gao, University of Washington
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"In
nanoparticles, one plus one is often less than two," Gao said. "Our
previous work showed that one plus one can be equal to two. This paper
shows that one plus one is, finally, greater than two."
The
first biological imaging, in the 1950s, was used to identify anatomy
inside the body, detecting tumors or fetuses. The second generation has
been used to monitor function – fMRI, or functional magnetic resonance
imaging, for example, detects oxygen use in the brain to produce a
picture of brain activity. The next generation of imaging will be
molecular imaging, said co-author Matthew O'Donnell, a UW professor of
bioengineering and engineering dean.
This
will mean that medical assays and cell counts can be done inside the
body. In other words, instead of taking a biopsy and inspecting tissue
under a microscope, imaging could detect specific proteins or abnormal
activity at the source.
But making this happen means improving the confidence limits of the imaging.
"Today,
we can use biomarkers to see where there's a large collection of
diseased cells," O'Donnell said. "This new technique could get you down
to a very precise level, potentially of a single cell."
Researchers
tested the method for photoacoustic imaging, a low-cost method now
being developed that is sensitive to slight variations in tissues'
properties and can penetrate several centimeters in soft tissue. It
works by using a pulse of laser light to heat a cell very slightly. This
heat causes the cell to vibrate and produce ultrasound waves that
travel through the tissue to the body's surface. The new technique
should also apply to other types of imaging, the authors said.
Co-authors
are UW postdoctoral researchers Yongdong Jin and Sheng-Wen Huang and
University of Michigan doctoral student Congxian Jia.
Research
was funded by the National Institutes of Health, the National Science
Foundation and the UW Department of Bioengineering.
Original article
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An external magnetic field attracts the nanoparticles by their magnetic cores. When the field is turned off, the tissue relaxes and the particles return to their initial positions. Credit: Xiaohu Gao, University of Washington
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