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All Together Now

Thanks to an unusually collaborative, cross-disciplinary research culture, Dartmouth boasts the most comprehensive and advanced effort anywhere to develop effective alternatives to mammography.

By Jennifer Durgin

Large, medium, small. Conical, round, elongated. Dense, fatty, fibrous. The wide variety of breast sizes, shapes, and compositions is more than just a cosmetic concern for women (or a curiosity for men, for that matter). That variability is part of why detecting cancer in breasts is so difficult and why mammography, for all of its merits, often falls short.

For all the breast cancers that mammography detects, many slip by unnoticed. And for all the abnormalities it identifies, only a small fraction of them turn out to be cancer. That results in a lot of women with undetected breast cancer and a lot more who experience the emotional and physical stress of a false alarm, also known as a false positive. Depending on a woman's age, family history, and other risk factors, as well as the skill of her radiologist, the chance of a false positive ranges from less than 1% to 98% on a first mammogram. After nine mammograms, it's estimated that 43% of women will have experienced a false alarm.

Add in the discomfort for many women of having their breasts compressed between two glass plates, plus the exposure of healthy breast tissue to ionizing radiation, and it's no wonder that some researchers are looking for a better screening method.

"I do mammography every day, and I strongly believe that it helps women," says Dartmouth radiologist Steven Poplack. "Unfortunately, what often gets quoted to the public is that mammography is 90% sensitive and we can find a cancer that is the size of a head of a pin, which is true in certain people." But that's not the whole story, he adds. "If you look at all comers, it's really not that sensitive. . . . Mammography has room for improvement and therefore the need for alternatives."

About 10 years ago, a group of engineers at Dartmouth's Thayer School of Engineering began exploring that need with the help of Poplack and others at Dartmouth Medical School. In 1999, the group secured a multiyear, $7.1-million program project grant from the National Institutes of Health (NIH) and began developing four different breast imaging technologies. In 2007, the collaboration—which now includes nearly 40 researchers at DMS, DHMC, and Thayer—was awarded a five-year, $7.7-million renewal from the NIH. At the end of this funding cycle, Poplack and his coinvestigator, Thayer engineer Keith Paulsen, hope to be able to move one or more of the imaging technologies into multicenter clinical trials.

The breast-imaging techniques being

developed at Thayer and DMS differ from mammography in that they focus on functional rather than structural information. One might say that mammography detects tissue that looks like a tumor, whereas the new Dartmouth modalities detect tissue that acts like a tumor.

For example, magnetic resonance elastography (MRE) uses an MRI scanner and specialized coils to measure the stiffness of breast tissue. "Almost all cancer is stiff," says John Weaver, Ph.D., a professor of radiology at DMS and the MRE project leader. "There is no other property that is so characteristic of cancer as increased stiffness." If MRE detects an area of the breast that is particularly stiff, or inelastic, that area might be a tumor—or so the hypothesis goes.

The other three alternative modalities exploit the electromagnetic spectrum to measure various tissue properties. (See here for a chart that details key point on the spectrum.) Two of the three—microwave imaging spectroscopy (MIS) and electrical impedance spectroscopy (EIS)—measure the ability of different regions of the breast to hold or conduct electricity. Part of what defines a tissue as cancerous is its architecture—how the cells and blood vessels are organized.

Legend:
Principal Investigators or Project Leaders
Faculty and Staff Collaborators
Graduate Students
Women Participating in the Clinical Trials


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Jennifer Durgin is Dartmouth Medicine's senior writer.

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