By using near-infrared light, which lies just outside the visible spectrum, researchers may soon be able to map the "optical signature" of breast tissue as a way of distinguishing between benign and malignant tumors. Although not yet ready for the clinic, optical mammography is being tested by several research groups and could obviate the need for biopsy in many women whose mammograms reveal suspicious lesions.
The new technology depends on the amount of blood hemoglobin present to detect a signature difference between benign and malignant tumors. If that difference is significant still a big "if" then optical mammography will enable physicians to shunt patients into high-risk and low-risk groups presumably with greater ease than a biopsy. Some 80% of breast biopsies are negative.
"Our goal is to characterize the optical properties of tumors," said Bruce Tromberg, Ph.D., who has built several prototype optical mammography
machines at the Beckman Laser Institute in Irvine, Calif. "It's not to necessarily find
tumors, but to find out if there are unique optical signatures in benign and malignant
tumors."
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The latest generation of optical devices builds on theoretical and technological advances in optical physics, using billionth-of-a-second bursts of light to divide absorption and scattering data which images deep breast tissue while yielding information on the amount of hemoglobin (the oxygen-carrying component of blood) present. Advanced versions of the technology may be able to detail levels of oxygen, water, and fat in breast tissue which may serve as critical clues for determining how threatening a tumor is.
But before those advances can materialize, researchers need baseline data on the optical signatures of breast tissue, which Brian Pogue, Ph.D., at Dartmouth College, Hanover, N.H., says can vary widely. Pogue is building what he calls a "fourth generation" optical mammography device and has imaged normal breast tissue and breast tumors. His data are preliminary, but it appears there is more hemoglobin in tumors than in normal breast tissue an important data point. Pogue is also trying to differentiate hemoglobin levels in known benign and malignant breast tumors.
Varied Applications
In a clinical study with pre- and post-menopausal women, Tromberg is finding that the optical signature of breast tissue changes with a woman's monthly and lifetime hormonal cycles; he says his device is so tuned to these changes that it can detect ovulation. (A future application may provide women with data to time their pregnancy-making efforts.) This hormonal sensitivity leads to another potential use for optical mammography, tracking response to hormone replacement therapy and chemopreventative drugs. To this end, Tromberg and his staff are imaging volunteers enrolled at the University of California-Irvine for the nationwide Study of Tamoxifen and Raloxifene STAR to follow their response to these drugs.
Dartmouth's Pogue sees a future treatment-tracking application as well. When (or if) antiangiogenic drugs become available, optical technology will be poised to image their effect. "Optical mammography is a perfect way to monitor antiangiogenesis, because what we're monitoring is blood," says Pogue. "As the blood vessels get killed off, we should see a decrease in the signal."
He added that optical mammography could be an alternative to x-ray mammography for younger women, as it is better able to image dense breast tissue. Traditional mammography can miss tumors in younger women for this reason. And while a large National Institutes of Health study is evaluating MRI's usefulness in finding tumors x-ray mammography may miss, optical mammography would be a much cheaper alternative, according to Tromberg, who said his prototypes cost about $20,000 to build. MRI machines cost upwards of $1 million.
Still Lab-Bound
For now, the most tantalizing near-infrared technologies remain lab-bound, even though several companies, including Siemens Medical Technology, Germany, and Philips Medical Systems, The Netherlands, have built optical mammography machines undergoing clinical testing (neither has received FDA approval). These early commercial devices were conceived as a kind of nonirradiating alternative to traditional mammography rather than a new technology to differentiate tumor types.
At Tufts University, Medford, Mass., Sergio Fantini, Ph.D., is collaborating with Siemens, collecting information on the optical signatures of possible tumors in 200 patients who had a suspicious mammogram. His preliminary data suggests that optical mammography detects just 75% of tumors found by biopsy. Some of the false negatives were out of the field of view of the machine, said Fantini, and his team is working to ferret out other reasons for the so-so detection rate.
"Very Preliminary"
Other experts, like Laurie Fajardo, M.D., head of the division of breast imaging at Johns Hopkins Hospital, Baltimore, are skeptical optical mammography will prove its worth in the field.
Fajardo said the images she's seen from commercial machines look "very preliminary and low-resolution." She sees more promise in linking existing imaging systems like MRI with advanced molecular markers that will highlight cancer cells. "We need the biochemists to catch up with the imaging technology," she said.
The physics of light-tissue interactions limits optical resolution to half a centimeter or so, much coarser than an MRI. But that isn't the point, say the researchers building the next-generation optical machines. They envision using optical technology as one part of an imaging suite, where a physician notices a suspicious spot on x-ray mammography, pinpoints its size and shape with ultrasound or MRI, and finally determines if it is malignant with optical mammography.
"Optical mammography will never displace conventional x-ray mammography," said Tromberg. "But it will be very complementary."
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