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Optical technique provides improved
'virtual biopsies' of internal surfaces
Applications may include scanning
for gastrointestinal tumors, vulnerable coronary plaques
BOSTON - November 19, 2006 - A new optical imaging technique,
developed at the Wellman
Center for Photomedicine at Massachusetts General Hospital (MGH),
can provide three-dimensional microscopic views of the inner surfaces
of blood vessels and gastrointestinal organs. In their report in
the journal Nature Medicine, receiving early online release
today, the MGH-Wellman researchers describe using optical frequency-domain
imaging (OFDI) to visualize broad areas of the esophagus and coronary
arteries of living pigs. The technique is an advance over optical
coherence tomography (OCT) - another noninvasive MGH-developed technology
that details much smaller areas - and could be useful for identifying
precancerous lesions and dangerous deposits of plaque in the coronary
arteries.
"For diagnosing early-stage disease, the clinician has been
basically looking for a needle in a haystack; so sampling only a
few microscopic points of an organ, as we could with OCT, is clearly
not sufficient," says Brett Bouma, PhD, of the MGH-Wellman
Center, the report's senior author. "With OFDI, we can now
perform microscopy throughout very large volumes of tissue without
missing any locations."
While OCT can examine surfaces one point at a time, OFDI is able
to look at over 1,000 points simultaneously by using a new type
of laser developed at MGH-Wellman. Inside the fiberoptic catheter
probe, a constantly rotating laser tip emits a light beam with an
ever-changing wavelength. Measuring how each wavelength is reflected
back, as the probe moves through the structure to be imaged, allows
rapid acquisition of the data required to create the detailed microscopic
images.
In the Nature Medicine paper, the MGH-Wellman team reports
that OFDI successfully imaged the inner esophageal surfaces of living
pigs, revealing the structural details and vascular networks of
4.5-centimeter-long segments with less than 6 minutes scanning time.
Scans of coronary artery surfaces were similarly successful, producing
three-dimensional microscopic images of the surfaces of segments
24 to 63 millimeters long. An experiment designed to evaluate OFDI's
ability to detect damage to arterial surfaces confirmed that the
technique could differentiate between healthy and damaged tissue.

In this optical frequency-domain image
of the coronary artery of a pig, the blue represents a metal stent
and the gray area shows whre the inner surface of the artery was
damaged.
Among potential applications for OFDI could be diagnosis of Barrett's
esophagus, a precursor to esophageal cancer that can be identified
with OCT, provided the affected tissue is scanned. The researchers
estimate that the esophageal scan conducted in this study could
be reduced from 6 minutes to less than 1 with more powerful computer
processing. Another major application would be examining coronary
arteries for the vulnerable plaques believed most likely to rupture
and produce heart attacks. A 2005
study from the MGH
Cardiology Division found that OCT could identify vulnerable
plaques in symptomatic patients, and the OCT-developed scanning
criteria could be used with OFDI to further study the vulnerable
plaque hypothesis and potentially to diagnose dangerous plaques
and guide their treatment.
The MGH-Wellman researchers also anticipate extending the technology's
capabilities into other fields. "One of the most exciting concepts
would be to directly link OFDI with the delivery of therapy, such
as laser treatment for early cancer," says Bouma. "Our
hope is that, thorough one minimally invasive probe, clinicians
will be able to diagnose and precisely treat diseased tissue while
sparing adjacent healthy tissue." Bouma is an associate professor
of Dermatology at Harvard Medical School.
A National Institutes of Health-funded clinical trial of OFDI to
monitor patients with Barrett's esophagus is currently underway
at MGH, and a trial of potential cardiovascular applications should
start up within the coming weeks. The current study was supported
by grants from the National Institutes of Health and from the Terumo
Corporation, which has licensed cardiovascular applications of OFDI.
The MGH is actively seeking an industrial partner to develop the
gastrointestinal applications. Several of the study's authors hold
patents related to aspects of OFDI technology.
Co-authors of the Nature Medicine report are first author
Seok-Hyun Yun, PhD, Guillermo Tearney, MD, PhD, Benjamin Vakoc,
PhD, Milen Shishkov, PhD, Wang-Yuhl Oh, PhD, Adrien Desgardins,
Melissa Suter, PhD, Raymond Chan, PhD, and Johannes de Boer, PhD,
all of MGH-Wellman; John Evans, MD, and Norman Nishioka, MD, MGH
Gastroenterology; and Ik-Kyung Jang, MD, PhD, MGH Cardiology. .
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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