Devices could help diagnose precursors to cancer
Deborah Halber, MIT News Office
Note: The following is based on an article that appeared in
the September 17, 2003 issue of TechTalk. The original can be located
at http://web.mit.edu/newsoffice/tt/2003/sep17/spectroscopy.html.
An MIT interdepartmental laboratory has received $7.2 million from
the National Institutes of Health (NIH) to further its work on devices
that can detect and image precancerous cells as noninvasively as
shining a tiny beam of light onto a patient’s tissue.
The George R. Harrison Spectroscopy Laboratory in the School of
Science has been awarded a Bioengineering Research Partnership grant
to develop and implement spectroscopic techniques for imaging and
diagnosing dysplasia—the precursor to cancer—in the
uterine cervix and the oral cavity.
Cervical and oral cancer account for approximately 11,000 deaths
in the United States each year and billions of health care dollars
in screening costs. Detection of the precancerous state of human
tissue is crucial for ease of treatment and greatly improved survival,
but it is often invisible and difficult to diagnose. The new techniques
provide a method for visualization and accurate diagnosis based
on spectroscopic detection and imaging.
Clinical screening for cervical and oral precancer are multibillion-dollar
industries which currently rely on visual detection of suspicious
areas followed by invasive biopsy and microscopic examination. Given
that visually identified suspicious areas do not always correspond
to clinically significant lesions, spectroscopic imaging and diagnosis
could prevent unnecessary invasive biopsies and potential delays
in diagnosis.
Furthermore, real-time detection and diagnosis of lesions could
pave the way for combined diagnosis and treatment sessions, thus
preventing unnecessary follow-up visits.
Michael S. Feld, professor of physics and director of the Spectroscopy
Lab, says the laboratory has developed a portable instrument that
delivers weak pulses of laser light and ordinary white light from
a thin optical fiber probe onto the patient’s tissue through
an endoscope. This device analyzes tissue over a region around 1
millimeter in diameter and has shown promising results in clinical
studies. It accurately identified invisible precancerous changes
in the colon, bladder and esophagus, as well as the cervix and oral
cavity.
The second device, which has not yet been tested on patients, can
image precancerous features over areas of tissue up to a few centimeters
in diameter.
The researchers hope that these new methods, which can provide
accurate results in a fraction of a second, may one day replace
tissue biopsies in diagnosing certain types of cancers.
Feld predicted that in a couple of years, these devices will lead
to a new class of endoscopes and other diagnostic instruments that
will allow physicians to obtain high-resolution images. These easy-to-read
images will map out normal, precancerous and cancerous tissue the
way a contour map highlights elevations in reds, yellows and greens.
The optical fiber probe instrument employs a method called trimodal
spectroscopy, in which three diagnostic techniques—light-scattering
spectroscopy (LSS), diffuse reflectance spectroscopy (DRS) and intrinsic
fluorescence spectroscopy (IFS)—are combined.
IFS provides chemical information about the tissue, LSS provides
information about the cell nuclei near the tissue surface and DRS
provides structural information about the underlying tissue. The
information provided by the three techniques is complementary and
leads to a combined diagnosis, though the imaging technique is based
on LSS alone.
These techniques have been developed over the past few years at
the MIT Laser Biomedical Research Center of the Spectroscopy Lab,
both directed by Feld. The center, an NIH resource for laser-related
medical research, is at the forefront for research using light and
spectroscopy for analyzing biological tissue.
The LSS optical technique has long been used to study the size
and shape of small spheres such as water droplets. For cancer detection,
the method is applied to the cell’s spheroid nucleus. Physics
theory predicts that scattered light undergoes small but significant
color variations when bouncing back from spheres of a certain size
and refractive index.
Light is delivered through the probe onto the patient’s tissue.
The probe collects the light that bounces back and analyzes its
colors. The color content is then used to extract diagnostic information.
“By analyzing the intensity variations in this back-scattered
component from color to color, the nuclear size and density can
be mapped,” Feld said. Closely packed cells with larger-than-normal
nuclei packed tightly with genetic material are markers of precancerous
change.
“The images created with this new technique are different
from ordinary microscopic images in that they provide hard and fast
information about cellular features,” he said. “We believe
this is an important step that will lead to new optical tools for
both [making] early cancer diagnoses and developing a better understanding
of how changes in the genetic material inside the cell’s nucleus
make the tissue more vulnerable to cancer.”
The NIH award, which is sponsored by the National Cancer Institute,
builds on diagnostic technologies that have been developed at the
spectroscopy laboratory over the past decade. Feld will head the
project and Kamran Badizadegan, a pathologist and cell biologist
at Massachusetts General Hospital (MGH), will be co-principal investigator.
MIT will pursue the research in collaboration with five institutions:
Boston’s Brigham and Women’s Hospital, for clinical
studies of cervical dysplasia; Boston Medical Center, for clinical
studies of oral dysplasia; MGH, for diagnostic pathology and development
of disease-specific spectroscopic markers; Harvard Medical School,
for development of disease-specific spectroscopic markers; and Chicago’s
Northwestern University, for development of novel spectroscopic
methodologies based on light-scattering spectroscopy.
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