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.
A version of this article appeared in MIT Tech Talk on September 17, 2003.