DURHAM, N.C. — For the first time, molecular events
below the skin can be seen not only in three dimensions, but in their true
color.
The new method developed by Duke University
bioengineers detects and shows in vivid shades of red the levels of hemoglobin
being carried by blood vessels, even the tiniest ones whose diameter can be as
narrow as a few red blood cells. Other molecules can also be visualized,
including medical dyes introduced to trace important biological mechanisms.
The developers of the technique believe it could have
significant implications both clinically and in basic science laboratories by
providing new perspectives on basic biological functions, including tumor
detection and eye disease.
To achieve this colorful view below the skin, the
bioengineers modified a technique that has been used by physicians and
researchers to provide cross-sectional images of biological tissues such as the
eye and gastrointestinal tract. The technique, known as optical coherence
tomography (OCT), uses scattered light or optical echoes to reconstruct the
structure underneath a tissues surface. As such, it is often referred to as
the optical equivalent of ultrasound.
“With conventional OCT we are able to see structures such as
blood vessels and even capillaries,” said Francisco Robles, graduate
student in the laboratory of Adam Wax, the Theodore Kennedy associate professor
of biomedical engineering at Dukes Pratt School of Engineering. “The main
drawback is that it doesnt provide some basic functional information,
including absorption which also gives the true color of the structures.”
The results of the Duke research, supported by the National
Institutes of Health, were published online by Nature Photonics.
“We expect that this new technique will have several
important applications, such as visualizing tumor development processes like
angiogenesis and oxygen deprivation,” Wax said. “It also could help in
detecting diseases of the eye, especially those that impact the tiny vessels of
the eye. It may have effectiveness in monitoring the delivery and effectiveness
of drugs.”
To achieve this ability to see true colors, Robles developed
a novel method for collecting and interpreting the information provided by the
OCT procedure to simultaneously include information regarding the wavelengths
or colors of light.
“Each point on the three-dimensional image that we collect
contains a great deal of useful information that we can use to reconstruct
whats happening at the molecular level,” Robles said. “The data not only help
create three-dimensional images, but it also contains important spectral
information.”
Blood, or more specifically the hemoglobin being carried by
red blood cells, provides the absorption that makes the process work. In a
sense, the hemoglobin, which caries oxygen, acts as a “natural” contrast agent
because of its absorption properties, which give blood its red color. Many
disorders can be characterized by the levels of blood oxygen, a characteristic
that can be detected in true shades of red by the new technique.
“The level of hemoglobin in tissue is very important,”
Robles said. “The additional information we can collect enables us to see
subtle shifts in hemoglobin levels, as well as changes in how the hemoglobin is
being distributed in local tissues.”
The Duke team tested the new system in living mice. When
conventional OCT was employed, certain structures – such as muscle and vessels
– could be observed. However, these images were black and white and couldnt
reveal information about the tissue function.
“With the new system, we observed a wealth of information we
couldnt before,” Robles said. “The muscle layer at the surface was relatively
colorless because of low hemoglobin levels. However, as the light continued
through the blood vessels below, a red shift in color was clear. To our
knowledge, these are the first micron-scale cross-sectional images of living
tissue in true color.”
The proprietary rights to the OCT technology are owned by
Oncoscope, Inc., a Durham-based company founded in 2006 by Wax based on the
Duke technology. Wax has a financial interest in the company.
Other Duke members of the team were Christy Wilson and
Gerald Grant.