Women’s Imaging: A New Dimension?
By Beth W. Orenstein
Radiology Today
Vol. 26 No. 8 P. 6

Study Underway to Determine 4D Mammography’s Breast Cancer Detection Potential

3D digital breast tomosynthesis (DBT) screening mammograms have shown to reduce the need for follow-up imaging compared with 2D mammograms. Could 4D mammography reduce the need for follow-up imaging or breast biopsies even further? That’s what a clinical trial underway at Baptist Health Hardin in Elizabethtown, Kentucky, is hoping to help determine.

The hospital is the first in the world to begin human trials of a new 4D mammography technology pioneered by Calidar Inc, a start-up formed out of Duke University in Durham, North Carolina. Calidar’s 4D technology uses X-ray diffraction to read molecular “fingerprints” in breast tissue to identify cancer.

“What we are measuring is X-ray scatter,” explains Stefan Stryker, PhD, cofounder and CEO of Calidar. “Scatter has always been there and normally it’s noise that blurs the 2D or CT data. But really there is a lot of useful information contained in that scatter, since it depends on the organization and structuring of the material it is passing through.”

What Stryker and colleagues Josh Carpenter, PhD, and Mitchell Greene have done is licensed and further developed a patented piece of metal placed between the patient and the detector. A reconstruction algorithm allows them to determine where the scattered X-rays come from. By measuring this scatter at the molecular level, it produces a unique “signature” that reflects the internal composition of the breast tissue, Stryker says. Unlike traditional X-ray images which rely on shape and density, he says, the technology reveals what the tissue is made of, not just what it looks like.

Stryker says some literature on the use of diffraction was published in the 1980s and 1990s, but those studies used low-energy sources. “What we are doing differently here is being able to actually measure that signature through volume,” Stryker says. He began work in this area when he started his PhD program in 2019, and Calidar has been working on applying it to 4D mammography for nearly four years.

Study Parameters
The trial at Baptist Health Hardin began in late August. Craig Kamen, MD, is the principal investigator and Bert Jones is the hospital’s director of medical imaging. The clinical trial aims to enroll 60 women who have had a 3D screening mammogram that found an abnormality 3 mm or larger that is at least 8 mm from the chest wall. Women must be 22 or older and cannot have had prior surgery or a malignancy of the breast. Potential participants are being identified internally, Jones says. The researchers expect the enrollment to take about six months.

Kamen believes that 4D mammography could help improve the cancer detection rate and views it as a complement to 3D. “It has the potential to decrease biopsy rate and callbacks following initial workups,” he says.

The research requires an extra craniocaudal view of the breast, followed by a targeted X-ray diffraction view to the area of interest on the mammogram. “All of this takes less than five minutes,” Kamen says. The mammography technologists participating in the research were given a short tutorial and “had no significant learning curve from what they normally do,” he adds.

The X-ray diffraction image will be postprocessed in the background with color mapping and a cancer classification score. “After the data collection for the study, a reader study will be conducted to quantify radiologist diagnostic performance reading conventional DBT images with and without having access to the X-ray diffraction cancer classification score,” Kamen says.

Jones adds that the acquisition is fairly similar to a traditional diagnostic mammogram. “The radiologist is consulted for the exact location of the abnormality, and this information is put into the system by the technologist,” he says. Jones believes technologists’ performance will likely improve as the technology is fine tuned.

Awaiting Results
Stamatia Destounis, MD, FACR, FSBI, FAIUM, chair of the ACR Commission on Breast Imaging and a member of Radiology Today’s editorial advisory board, says it is too soon to determine whether Calidar’s 4D technology is promising.

Kamen and Jones, however, are optimistic. “The technology was initially approved for lumpectomy samples and surpassed the expectation,” Jones says. “We look for this first human study to be the same.”

If the technology proves successful in this and subsequent trials, it could revolutionize how breast cancer is detected and diagnosed, Stryker says. Kamen says they are in the early phase of the study, and he is looking forward to sharing the results within a year or so.

Stryker says Calidar’s current focus is strictly on breast imaging and improving breast cancer imaging, but he hopes that in the future it will have applications for screening for other cancers and diseases. Jones adds that the technology could eventually be rolled out to other modalities such as CT and plain film X-ray.

Stryker is from Lexington, Kentucky, and local connections brought him to Baptist Health Hardin to become the first hospital in the world to begin in-human trials of the new 4D mammography technology. Jones says that the hospital was honored to be participating in this first-in-human clinical trial focusing on advancing care for mammography patients. Baptist Health has a large women’s imaging presence in central Kentucky and “We had the space and personnel to carry out the study,” Jones adds. Baptist Health Foundation Hardin supported the project by funding a portion of the necessary renovations to house the new 4D mammography equipment and services that are needed.