By Vivian Cooper-Capps
January 17, 2002

The stakes in brain surgery are extremely high: If a surgeon removes as little as a millimeter of healthy tissue, the patient can be permanently impaired, but leave behind just a few malignant cells and the patient may die.

Even when armed with sophisticated computerized pre-operative scans, finely honed skills and the experience of decades of successful operations, brain surgeons find it extremely difficult to locate the border between diseased and healthy brain tissue. So, it's little wonder that the surgical community is excited about the research of Anita Mahadevan-Jansen.

The assistant professor of biomedical engineering has developed optical techniques that use laser probes to discriminate between healthy and diseased tissue. These techniques can give surgeons precise assessments of tissue health as they operate, without having to wait for time-consuming and costly laboratory tests.

Her optical spectroscopic techniques can also be used to quickly diagnose and monitor treatment of the cervix, ovaries and skin, without requiring invasive biopsies that hurt and take a long time to deliver results.

"Our brain research so far is very promising," says Mahadevan-Jansen. "The optical surgical guidance system we've developed has achieved nearly 100 percent accuracy in identifying the margins of brain tumors."

The system has proven superior to even the experienced eye. "Several times our techniques have indicated that the surgeon had not quite gotten the entire tumor, and the histological results of the laboratory proved that the optical [guidance system] data was correct."

The technique, pioneered by Mahadevan-Jansen with funding from the National Institutes of Health, uses two light sources: broadband white light and the light produced by a nitrogen laser, which causes certain molecules in the body to fluoresce. Both are delivered to the area under study by a slender fiberoptic probe.

"We use reflectance data from the white light to account for blood and the fluorescence data to give us a sense of the biochemistry and morphology of the tissue," she says.

The tissues are analyzed by comparing the patterns of how the tissue reflects, absorbs or scatters the two different types of light with the known patterns of normal and cancerous tissue.

Mahadevan-Jansen and her team did several months of in vitro research to characterize the differences in the reflected and fluorescent light obtained from normal and tumor tissues. Next, the assessment techniques were applied in the operating room and the equipment was redesigned to make it more portable. The redesigned equipment was then tested in more than 70 brain surgeries performed at Vanderbilt Hospital and, beginning last fall, it has been used to guide brain biopsies at M.D. Anderson Hospital in Houston, Texas.

In the future, Mahadevan-Jansen hopes to adapt the approach so it will work as a guidance tool in diagnosing and removing cancers of the liver, skin and prostate.

To diagnose cancers of the ovaries and cervix, Mahadevan-Jansen is using a different optical technique based on Raman spectroscopy. "We found that using fluorescence was not as accurate as using Raman scattering; because fluorescence produced too many false positives," she says.

Raman spectroscopy measures the vibrational energies of the tissue's molecules. "Most photons enter and exit tissue at the same wavelength, or energy level," Mahadevan-Jansen says. "But a small fraction of light emerges in directions other than the incoming beam, with greater or less energy than the initial light. We measure those frequency shifts and produce a pattern that is characteristic of particular molecular species."

Like the equipment used in the brain research, Raman spectroscopy uses a laser light source, fiber to deliver the light and return data through a probe, a spectrograph to measure the data, a digital camera to record the data and a computer to control the process and graphically present the results.

The Raman spectroscopy technique is being extensively developed and clinical trials have begun at Vanderbilt Hospital.

"Right now we're producing spectral data on graphs in all our optical spectroscopy projects," Mahadevan says. "But we are also adapting our techniques to use spectral imaging technology, a new image modality that gives spatial information as well as spectral information."

Mahadevan-Jansen is also adapting her Raman spectroscopy techniques to diagnose middle-ear infections and to measure cholesterol levels without drawing blood samples. She has also built a Raman micro-spectrometer which, unlike cervical and ovarian systems, does not contact the tissue but is capable of focusing through the tympanic membrane or the surface of the skin.

Prof. Mahadevan-Jansen's home page:
http://www.vuse.vanderbilt.edu/~anitha/myworld.htm

Biomedical Optics Laboratory website:
http://www.bme.vanderbilt.edu/bmeoptics/newindex.html