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July 16, 2007

Cone Beam CT — A 360° Alternative to Mammography
By Beth W. Orenstein
Radiology Today
Vol. 8 No. 14 P. 10

Researchers at UC Davis found they could produce high-quality CT images of the breast at radiation levels comparable to or less than mammography.

Despite widespread mammography screening programs, breast cancer remains the second leading cause of cancer death among women in the United States. (Lung cancer is still No. 1.) Mammography has helped to reduce mortality by as much as 20% to 35% in women aged 50 to 69 and slightly less in women aged 40 to 49. Yet each year in America, 40,000 women die from breast cancer.

The problem is that mammography, even when performed by the best mammographers in the world, is still only 85% accurate. A mammogram is taken through all the layers of the breast at once and is less sensitive in women with dense or glandular breasts. Younger women tend to have dense breasts, and cancers that strike younger women tend to be more aggressive.

“Everything in the breast is white,” says Avice O’Connell, MD, MRCPI, director of women’s imaging and associate professor of imaging sciences at the University of Rochester Medical Center (URMC) in New York. “Normal breast tissue is white. Cysts are white. Fibroadenomas are white. Cancers are white like almost everything else. It’s like we are searching for a snowman in a snowstorm.”

Mammography also compresses the breast, producing a 2-D image, making it even harder to find a white abnormality on a white background, O’Connell says.

Same Old Problem
That’s why the search continues for another imaging modality that would be more effective for screening and diagnosing the roughly 50% of women with dense breast tissue. Dense breasts also are considered a risk factor for breast cancer, O’Connell says.

Recently, MRI has shown to be a better tool for detecting early stage tumors in women with dense breast tissue. The evidence is strong enough that in March, the American Cancer Society updated its recommendations, urging women at high risk for developing breast cancer to alternate screenings at six-month intervals between mammography and breast MRI.

MRI also has been found to detect cancers in the contralateral breast that may be missed by mammography and clinical examination at the time of the initial breast cancer diagnosis. A study of 969 women that was published in The New England Journal of Medicine in March found that MRI detected clinically and mammographically occult breast cancer in the contralateral breast in 30 (3.1%) of them.

However, breast MRI costs more—approximately 10 times more than mammography—and is not always widely available. MRI also has some issues with magnet safety in women with implanted medical devices or claustrophobic issues.

Meanwhile, researchers at several sites, including URMC and the University of California (UC), Davis in Sacramento, have been studying yet another tool—cone beam CT—that could be better at detecting early stage cancer in some women than mammography and possibly MRI.

Prototypes in Trial
A start-up company in Rochester, Koning Corporation has raised nearly $11 million and built a breast cone beam CT scanner prototype specifically for imaging breast tissue. Its research funds include a $2.5 million grant from the National Institutes of Health (NIH). It has built a prototype scanner designed by Ruola Ning, PhD, a professor in the URMC department of radiology who has been working on cone beam CT for the past 14 years.

The UC Davis team built two prototype scanners with $6 million in grants from the NIH and California Breast Cancer Research Program. “We’re ready to transition to a second scanner in the next month or so,” says John Boone, PhD, a medical physicist who is working on the project with radiologist Karen Lindfors, MD. The differences between the two UC Davis prototype scanners are mostly technical, Boone notes. “The new scanner is bigger and has more power.”

In 2004, the UC Davis team, with Boone and Lindfors as principal investigators, became the first group to begin clinical trials with its breast scanner. They began a phase 2 clinical trial that will enroll a total of 190 women. They opened the trial to UC Davis patients who have had mammograms suspicious for breast cancer and would undergo needle biopsy to confirm the presence of cancer. To date, the team has imaged more than 120 women including 10 healthy volunteers, and Lindfors has finished evaluating most of them.

CT is used every day for scanning heads, lungs, abdomens, and pelvises, but it had not been seriously considered for breast cancer screening because of long-held misconceptions that very high radiation doses would be needed, Boone says. The old thinking was based on use of standard CT machines, which would require the breast and entire chest to be scanned together, Boone explains. The UC Davis researchers not only questioned that dogma but also proposed a scanner design that would image only breast tissue, thus reducing the radiation dose required.

By using computer simulations and performing experimental measurements on cadavers, the researchers at UC Davis found they could produce high-quality CT images of the breast at radiation levels comparable to or less than mammography.

Radiation Dose
The Rochester researchers have also been able to produce images with their CT scanner using radiation dose levels comparable to currently practiced two-view mammography. “We looked at the diagnostic mammography of our study group, and the range went from 3.9 to 15.6 milligray (mGy) with a mean of 10 mGy for a diagnostic exam,” O’Connell says. “In our CT exams, the dose ranged from 4.3 mGy to 16 mGy, with a mean of 9.9 mGy, so that’s pretty close. There is a range and it is not that much different from a mammogram.”

O’Connell says that even at those doses, the resolution was very high, and the images were of excellent quality, making the research team very optimistic. “In one case of a known cancer, we thought we saw the cancer better with the CT and that we could see an extension of the cancer that we didn’t see on the mammogram,” she says.

Some patterns of calcifications, such as tight concentrations and irregular shapes, can suggest a malignancy. The cone beam CT scanner is better at detecting microcalcifications than MRI, O’Connell says. Boone says that mammography is still better at finding microcalcifications than breast CT, but the researchers are looking at solving that issue by making some x-ray spectral changes and by making smaller voxels.

Boone believes the CT cone beam scanner will eventually prove better to detect smaller cancers than mammography, technology that was developed in the 1950s.

“We think CT will allow the detection of breast cancer lesions in the 3- to 5-millimeter range, although this has not been proven yet,” Boone says. “That is about twice as small as the typical tumor seen by conventional mammography.”

If CT is able to detect smaller cancers, it would be highly significant, Boone says, because the earlier and smaller a malignancy is when it is detected, the lower the chance that it has spread to the lymph nodes, lungs, or bones. When detected early, there is a greater opportunity for a permanent cure and breast preservation, he says.

Rochester’s CT scanner takes roughly 10 seconds to image a breast. The woman lies flat on the table and places her breast in a hole in the specially built table, and the x-ray tube rotates around the breast at 360° collecting all the images. It generates about 300 to 500 images of the breast.
“The computer takes those images and does a beautiful reconstruction of the breast,” O’Connell says. “The pictures produce a 3-D image, and you can look at it from every angle. Thanks to the wonders of computers, the images are gorgeous. They look like a model of the breast.”

Breast Not Compressed
One of the biggest advantages of CT vs. mammography, O’Connell says, is that the breast is not compressed. Not only does it mean the patient is more comfortable during the screening but also that the images are 3-D, making them more useful.

Boone says the UC Davis scanner, which takes roughly 10 to 17 seconds to scan a breast, currently does not provide the depth of coverage of the woman’s chest wall that MRI does. However, he says, the team is trying to redesign the padded table so the patient’s chest wall is included in the scan field. More extensive clinical trials will be needed before the scanners would be available clinically, Boone says.

O’Connell says the scanners should be tested not only in trials against mammography and MRI but also against digital tomosynthesis, another technique under development that also takes multiple x-ray images of each breast with less overlap. With digital tomosynthesis, the x-ray tube moves in an arc around the breast while 11 images are taken during a 7-second examination. However, slight pressure must be applied to the breast to keep it from moving during the procedure. “It will be interesting to study the same ladies with breast CT and with tomosynthesis,” Boone adds.

Boone says breast CT may not prove useful for routine screening in the absence of contrast. However, he says, he has no doubt that it will be useful in treatment planning for women who are diagnosed with breast cancer.

“If someone comes in and has a mammogram and something is found to be suspicious on those films,” he says, “they’ll call her back and do some additional views, maybe ultrasound and perhaps contrast enhanced MRI. I can see where breast CT may have a role to play in a scenario like this as well.”

Possible Biopsy Use
Breast CT also could be useful in biopsy and could perhaps replace the stereotactic biopsy table that can be cumbersome and painful for patients, Boone says. Researchers first considered and tested a prototype breast CT scanner in the 1970s, but it was abandoned as impractical. Researchers at the University of Massachusetts and Duke University also are developing breast CT prototypes.

“At this point,” O’Connell says, “no one can say which modality is better or best at detecting early stage breast cancer. It will take many more trials to know. Cone beam CT is going to have to stand up to proper scientific review where multiple independent readers evaluate it.”

O’Connell says it would not be worth investing all the time and money into developing a cone beam CT scanner for the breast “if it didn’t have the potential to significantly improve on what we’re doing now.” But the preliminary indications are that it may have that potential, she says, and that’s exciting.

— Beth W. Orenstein is a freelance medical writer and regular contributor to Radiology Today. She writes from her home in Northampton, Pa.

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