Researchers
at the Massachusetts Institute of Technology (MIT) have developed a new
imaging system that enables high-speed, three-dimensional (3-D) imaging
of microscopic pre-cancerous changes in the esophagus or colon. The new
system, described in the Optical Society’s (OSA) open access journal
Biomedical Optics Express, is based on an emerging technology called
optical coherence tomography (OCT), which offers a way to see below the
surface with 3-D, microscopic detail in ways that traditional screening
methods can’t.
Endoscopy
is the method of choice for cancer screening of the colon or esophagus.
In the procedure, a tiny camera attached to a long thin tube is snaked
into the colon or down the throat, giving doctors a relatively
non-invasive way to look for abnormalities. But standard endoscopy can
only examine the surface of tissues, and thus may miss important changes
occurring inside tissue that indicate cancer development.
OCT,
which can examine tissue below the surface, is analogous to medical
ultrasound imaging except that it uses light instead of sound waves to
visualize structures in the body in real time, and with far higher
resolution; OCT can visualize structures just a few millionths of a
meter in size. Over the past two decades, OCT has become commonplace in
ophthalmology, where it is being used to generate images of the retina
and to help diagnose and monitor diseases like glaucoma, and has
emerging applications in cardiology, where it’s used to examine unstable
plaques in blood vessels that can trigger heart attacks.
The
new endoscopic OCT imaging system reported by OCT pioneer James G.
Fujimoto of MIT and his colleagues, works at record speeds, capturing
data at a rate of 980 frames (equivalent to 480,000 axial scans) per
second—nearly 10 times faster than previous devices—while imaging
microscopic features less than 8 millionths of a meter in size.
At
such high speeds and super-fine resolution, the novel system promises
to enable 3-D microscopic imaging of pre-cancerous changes in the
esophagus or colon and the guidance of endoscopic therapies. Esophageal
and colon cancer are diagnosed in more than 1.5 million people worldwide
each year, according to the American Cancer Society.
“Ultrahigh-speed
imaging is important because it enables the acquisition of large
three-dimensional volumetric data sets with micron-scale resolution,”
says Fujimoto, a professor of electrical engineering and computer
science and senior author of the paper.
“This
new system represents a significant advance in real-time, 3-D
endoscopic OCT imaging in that it offers the highest volumetric imaging
speed in an endoscopic setting, while maintaining a small probe size and
a low, safe drive voltage,” says Xingde Li, associate professor at the
Whitaker Biomedical Engineering Institute and Department of Biomedical
Engineering at Johns Hopkins University, who is not affiliated with the
research team.
In
OCT imaging, microscopic-scale structural and pathological features are
examined by directing a beam of light on a tissue and measuring the
magnitude and echo time-delay of backscattered light. Because the amount
of light that can be recaptured and analyzed decreases quickly with
depth in tissue due to scattering, the technique can generally only be
used to visualize sub-surface features to a depth of 1 to 2 millimeters.
“However these depths are comparable to those sampled by pinch biopsies
and unlike biopsy, information is available in real time,” Fujimoto
says. By using miniature fiber optic scanning catheters or probes,
either on their own or in combination with standard endoscopes,
colonoscopes, or laparoscopes, OCT imaging can be performed inside the
body.
In
collaboration with clinicians at the VA Boston Healthcare System and
Harvard Medical School, the team is investigating endoscopic OCT as a
method for guiding excisional biopsy—the removal of tissue for
histological examination—to reduce false negative rates and improve
diagnostic sensitivity.
“Excisional
biopsy is one of the gold standards for the diagnosis of cancer, but is
a sampling procedure. If the biopsy is taken in a normal region of
tissue and misses the cancer, the biopsy result is negative although the
patient still has cancer,” notes Fujimoto, whose team is one of a
number of research groups—including at Johns Hopkins University; the
University of California, Irvine; Case Western University; and
Massachusetts General Hospital—that are actively pursuing the
development of smaller, faster endoscopic OCT systems.
Endoscopic
OCT requires miniature optical catheters or probes—just a few
millimeters in diameter—that can scan an optical beam in two dimensions
to generate high-resolution 3-D data sets. Scanning the beam in one
transverse direction generates an image in a cross-sectional plane,
whereas scanning the beam in two directions generates a stack of
cross-sectional images—that is, a 3-D (or volumetric), image.
“This
device development is one of the major technical challenges in
endoscopic OCT because probes must be small enough so that they can be
introduced into the body, but still be able to scan an optical beam at
high speeds,” Fujimoto says. “Increasing imaging speeds has also been an
important research objective because high-resolution volumetric imaging
requires very large amounts of data in order to cover appreciable
regions of tissue, so rapid image acquisition rates are a powerful
advantage.”
The
optical catheter developed by the MIT researchers and their
collaborators uses a piezoelectric transducer, a miniature device that
bends in response to electrical current, allowing a laser-light emitting
optical fiber to be rapidly scanned over the area to be imaged.
So
far, the device—which must be further reduced in size, Fujimoto notes,
before it can be deployed with the standard endoscopes now used—has only
been used in animal models and in samples of human colons that had been
removed during surgical procedures; further development and testing of
the technology is needed before it can be tested in human patients. “The
ultimate clinical utility of new devices must be established by large
clinical studies, which assess the ability of the technology to improve
diagnoses or therapy,” he says. “This is a much more complex and lengthy
task than the initial development of the technology itself.”
