CEMammogram.net | Contrast Enhanced Mammography Mammogram

CEM Basics

CEMammogram.net provides information and resources about a powerful new type of breast imaging, contrast enhanced mammography (CEM), which is also referred to as contrast enhanced spectral mammography (CESM), contrast enhanced digital mammography (CEDM), and CE-mammography (CE-mammogram). Hundreds of peer-reviewed clinical studies show that CEM has a greater cancer detection rate than 2D digital mammography and 3D mammography (also known as digital breast tomosynthesis/DBT). Clinical studies also show that CEM has a similar cancer detection rate to breast MRI, but CEM is a faster and less expensive exam than full breast MRI. A recent study shows that 71% of women polled prefer CEM over breast MRI for supplemental breast imaging.

CEM is a particularly advantageous imaging study for women with dense breast tissue and women at elevated risk of breast cancer. This is because dense breast tissue can obscure cancers on digital mammograms and 3D mammograms. The CEM exam “subtracts away” the dense tissue which helps show if a suspicious or possibly malignant lesion may be present. Just as importantly, CEM can also help radiologists quickly determine if there are no concerning lesions present, which can give both the patient and her healthcare team additional peace of mind.

How does CEM work?

Contrast-enhanced mammography (CEM) is a breast imaging technique that uses an iodine-based intravenous (IV) contrast agent in combination with a special type of “spectral” 4-view mammogram. The IV-contrast injection and spectral imaging makes it easier to see new blood vessels which form when cancers grow. This is known as "angiogenesis" whereby fast growing tumors form "leaky" blood vessels which allow the injected IV-contrast material to pool around the tumor and show up on the CEM images.

From the patient’s perspective, the CEM mammogram is very similar to a regular 2D digital mammogram or 3D mammogram. However, prior to being positioned on the mammography gantry and having compression applied to the breast, an IV-needle is placed in the arm of the patient and then an injection of iodinated contrast material is given. This IV-injection step is essentially identical to that used for a “with contrast” CT exam, which is safely performed more than 40 million times per year in the USA.

For each of the 4-mammogram views, two images are acquired in rapid succession using different x-ray parameters. It is nearly imperceptible that two images are being acquired rather than one (but the patient does need to hold very still for a few seconds). A sophisticated image reconstruction algorithm then “subtracts” the two images from one another, which helps to remove the dense breast tissue. The resulting CEM image will either (1) show if there is an area of tissue which has accumulated the IV contrast material (“dye”) and is thus indicative of cancer; or (2) will show no IV contrast material accumulation … which indicates that no suspicious areas or possible malignancies are present.

“Your Contrast Mammogram - What to Expect,” https://www.youtube.com/watch?v=cu7TsR4NtIg

This 3.5 min video shows the entire CEM process including IV-injection, CEM acquisition, interpretation, and consultation.

What do CEM images look like?

The standard four mammographic views are typically acquired with each CEM study: Right CC, Left CC, Right MLO, Left MLO. (CC = craniocaudal view and MLO = mediolateral oblique view). For each of these "views" ... two different images are generated for the radiologist to review. The first is a typical digital mammogram which shows all of the breast anatomy including skin line, nipple, chest wall, pectoral muscle, dense tissue (i.e. breast glands and breast ducts), fat, blood vessels and other internal connective tissue. This digital mammogram image is also referred to as the "low energy" image. The second image that the radiologist sees is the "subtracted" or "recombined" image which will have the majority of the dense breast tissues removed. A third image is generated by the system, the "high energy" image, but this is not viewed by the radiologist. In total, a routine CEM exam generates eight images for the radiologist to view (see below example). Occasionally, additional views are added to the CEM acquisition, such as a true lateral view of one or both breasts.

One of the things that makes CEM such a powerful and confidence inspiring tool for radiologists is that the study generates both traditional digital mammogram images which yield high quality, reliable anatomical information, and the "subtracted" CEM images which give highly sensitive physiologic information similar to that generated by breast MRI. It is the combination of these two types of images that gives CEM studies both excellent cancer detection power and superb accuracy (i.e. both high "sensitivity" and high "specificity"). The conventional digital mammogram images generated by the CEM study are also very good at depicting if there is a cluster of microcalcifications present. Microcalcifications are sub-millimeter sized specs of calcium which are indicative of ductal carcinoma in situ (DCIS), a form of early breast cancer.

Diagnostic CEM exam: The left column above shows the "low energy" digital mammogram images produced by a CEM exam, the right column above shows the "subtracted" CEM images. Note how the bright white dense fibroglandular tissue shown in the low energy digital mammogram images on the left has been removed from the subtracted CEM images on the right, allowing much better visualization in the LCC and LMLO images of multiple enhancing areas which are indicative of malignancy and may require biopsy (tissue sampling for pathologic study). The larger enhancing area in the subtracted CEM images is somewhat apparent on the digital mammogram images on the left. However, the smaller so-called "satellite" lesions are obscured by the dense tissue in the digital mammogram images on the left, but they are quite apparent in the CEM images on the right.

How does one get a CEM exam?

The patient's radiologist in consultation with her primary care physician and/or other healthcare professional determines if a CEM exam is needed. CEM is a type of “diagnostic mammography” and requires pre-authorization from the health insurance / healthcare coverage provider, and a prescription / referral from the patient’s primary care physician, just like breast MRI and breast ultrasound require. However, CEM is usually authorized by insurance companies in a rapid timeframe whereas a breast MRI exam can take up to two weeks or longer for health insurance to authorize. In many instances, CEM may be performed during the normal screening mammogram visit if the radiologist deems CEM is necessary due to the presence of an area of concern and/or significant dense tissue.

Women whose mammography report says they have dense breast tissue (either BIRADS C: heterogeneously dense or BIRADS D: extremely dense) and women at an elevated risk of breast cancer should speak to their physician and mammography provider about supplemental imaging with CEM. Please go to the "CEM Providers" page of this website for a state-by-state directory of sites that perform contrast enhanced mammography (CEM) studies.

What happens if CEM finds something?

If a suspicious area is visualized on the CEM study, the radiologist may recommend the patient be referred for a breast biopsy so that the area can be sampled with a needle and the tissue then sent to a pathologist for a definitive diagnosis. Often, areas detected with CEM can be biopsied using ultrasound guidance or stereo/3D mammography guidance. However, occasionally the lesion seen with CEM can not be found with ultrasound or traditional stereo/3D biopsy. In these cases, a CEM-guided biopsy may be required. The process for CEM-biopsy is identical to a traditional stereo biopsy, however prior to the breast being compressed and needle inserted, an IV-injection is administered to the patient, just as with a diagnostic CEM study. CEM-guided biopsy is a quick and efficient outpatient procedure and usually takes less than half an hour for the entire exam.

Diagnostic CEM case and CEM-guided biopsy: the image above on the left is the low energy digital mammogram showing an area of dense tissue. The center image is the CEM subtracted-view showing a 5 mm nodule with IV-contrast uptake (pink circle). This lesion was not visible on ultrasound so US-guided biopsy could not be performed. Thus the radiologist performed CEM-guided breast biopsy of the nodule. The upper right image shows the biopsy needle just prior to sampling the enhanced nodule. The lower right image shows the biopsy marker clip deployed at the biopsy site after the tissue sample has been removed. The biopsy procedure time with the breast in compression was approximately 10 minutes from start of the IV-injection to deployment of the clip; and the entire procedure including patient preparation and initial post procedure care took about 30 minutes. The pathologist's examination of the sample returned a diagnosis of invasive ductal carcinoma.

CEM-guided biopsy is a relatively new capability and some sites that are performing diagnostic CEM do not yet have CEM-guided biopsy capability. In the cases where the lesion can not be found with ultrasound or stereo biopsy, the patient would be referred for MRI guided breast biopsy or to a location that has the CEM-guided biopsy capability.

Some sites that have CEM-biopsy capability will use it to biopsy areas of concern identified with breast MRI. CEM biopsy is a much faster procedure than MRI biopsy, is better tolerated by patients, and CEM biopsy is very accurate. CEM biopsy can also be combined with 3D mammography/stereo biopsy of microcalcifications, another type of abnormality that is highly indicative of cancer.

Other uses of CEM

In addition to use as a supplemental imaging exam for women with dense breasts, CEM is a very capable tool and is used in a similar fashion to breast MRI for a variety of needs:

Diagnostic workup of a lump or other suspicious area
Determine extent of disease in both breasts if cancer is diagnosed
Track tumor response to neoadjuvant chemotherapy
Surgical planning
Post treatment surveillance, CEM is very helpful to image the breast following lumpectomy to look for recurrence and does not struggle to penetrate scar tissue as do digital mammography and 3D mammography

What are the alternatives to CEM and pros and cons of each?

Mammography (2D and 3D) is the FDA approved and widely available technology used to screen for breast cancer in women aged 40 and above. Mammography is a very good test and it has been shown to reduce mortality from breast cancer and improve outcomes when cancers are found earlier and smaller. But as discussed above, both 2D and 3D mammography struggle with dense breast tissue, especially in extremely dense breasts. The primary methods of breast imaging used to supplement mammography for women with dense breasts are (1) whole breast ultrasound, (2) breast MRI, and (3) contrast enhanced mammography. Each has pros and cons.

Whole breast ultrasound can be performed with nearly all of the handheld breast ultrasound systems in use or with automated breast ultrasound systems. The benefits of whole breast ultrasound are that it is widely available, is covered by many insurance providers, has no radiation, is performed without any IV-injections, it does not require breast compression, and whole breast ultrasound plus mammography provides added cancer detection on top of mammography / 3D mammography alone (8 cancers per 1,000 patients versus 6 cancers per 1,000 patients). Ultrasound is also a great tool for guiding the biopsy of suspicious masses. The downside of whole breast ultrasound is that it has the lowest cancer detection rate of the three supplemental imaging modalities discussed here, it provides anatomical information but no physiological information, it is time consuming to interpret, and it is more prone to false positive findings than CEM.

Breast MRI is considered by many to be the "gold standard" in supplemental imaging for women with an elevated risk of breast cancer, it has the highest cancer detection rate, it does not use ionizing radiation, does not require breast compression, has superior performance visualizing the chest wall and axilla, and it has been in use since the 1990s and is a well established modality. The downside of breast MRI is that it is a longer examination that requires the patient to lie face down for 26 minutes on average (plus time to place the IV-needle and administer the contrast injection and then remove the IV afterwards), it is contraindicated (not available) for patients with certain implants or claustrophobia, it requires an IV-injection of gadolinium contrast material (which some patients have contraindications to), it is expensive and can take up to two or more weeks to get insurance to approve, it usually requires the patient to go to a different location/facility than the mammography center, it is time consuming to interpret, and it is more prone to false positive findings than CEM. Breast MRI is used to successfully guide the biopsy of lesions, but MRI guided breast biopsy can take up to an hour to perform with the patient lying face down. A growing number of locations are performing a new abbreviated breast MRI which can be completed in half the time of full diagnostic breast MRI. However, many insurance companies will not reimburse for abbreviated MRI and thus women have to pay out of pocket to have it. (Note: the time to perform full diagnostic breast MRI varies widely, a recent journal article reports that depending on the protocol used, image acquisition times range from17 minutes to 35 minutes, not including the time needed for IV-needle placement and removal, or time needed for the patient to get on and off of the table/breast coil. The time to perform abbreviated breast MRI also varies widely, depending on site and protocol used.)

Contrast Enhanced Mammography (CEM) has many advantages: it is a fast exam taking only 7 minutes to acquire the images (plus time to place the IV-needle and administer the contrast injection and then remove the IV afterwards), it has a cancer detection rate/sensitivity that is similar to breast MRI, CEM is relatively inexpensive and rapidly approved by health insurance providers, CEM can often be performed the same day as a screening mammogram appointment, CEM has a low false positive rate and a very high negative predictive value (i.e. it is very accurate at indicating when there is no cancer present). Further, CEM is performed right on the same mammography machine that routine 2D and 3D mammograms are performed on by the same mammography technologists that the woman already knows. And CEM-guided biopsy is a very fast and accurate exam that is performed with the patient sitting upright and is preferred by most patients and radiologists alike. The downsides of CEM are that it uses low dose x-ray radiation (a bit more than a 2D mammogram but a bit less than a typical 3D mammogram, which is usually acquired together with a 2D mammogram), it requires an IV-injection of iodinated contrast (which some patients have contraindications to), CEM requires breast compression as with conventional mammography, and CEM is not yet widely available. Although CEM has been evaluated in hundreds of clinical studies, breast MRI has a longer track record: CEM has been in clinical use since late 2011 (approx.12 years) and bilateral breast MRI has been in clinical use since 1991 (approx. 32 years). However, a recent survey shows that when presented with all the pros and cons of each, nearly three out of four women who had both studies prefer CEM to breast MRI.

DenseBreast-Info has created a handy chart which compares the incremental breast cancer detection rate of breast ultrasound, breast MRI, and CEM. https://densebreast-info.org/screening-technologies/for-patients-screening-tests-after-a-mammogram/

Patient perspective: CEM vs. Breast MRI (durations shown do not include time needed to place IV-needle and administer injection).

Upper row: comparison of diagnostic exams

Lower row: comparison of biopsy procedures

Brief history of the development and current state of CEM

The initial development of contrast enhanced mammography (CEM) started in the late 1990s and gained momentum when full field digital mammography became available in 1999. The first clinical CEM product using spectral/dual energy imaging was FDA-cleared for use as a diagnostic exam in 2011 (GE HealthCare SenoBright). The peer-reviewed results of a multireader study of CESM performed in France were published showing an improvement in sensitivity (finding additional cancers) and specificity (reducing false positives) versus standard digital mammography. However, despite these promising results, initial adoption of CEM was slow as US radiologists waited for additional clinical validation of CEM over a larger population of patients. Further, a few months prior to the launch of CEM, 3D mammography (AKA digital breast tomosynthesis) had been FDA approved. The approval of 3D mammography was tied to a multi-center clinical trial which validated its performance over a relatively large patient population. This helped spur the rapid adoption of 3D mammography. In addition to competing with 3D mammography for mind share and hospital budget, when CEM was launched in 2011 it was viewed with some skepticism versus breast MRI which had been refined over the prior two decades of clinical use and was seen as the "gold standard" of supplemental imaging for women with dense breasts. Nonetheless, even though CEM started out in the shadow of 3D mammography and breast MRI, early adopters around the world saw the tremendous promise in CEM and began to implement and conduct clinical studies of the technology.

(Great thanks and sincere commendation to the physicians and researchers who drove the early development and clinical implementation of CEM including Dr. John Lewin, Martin Yaffe PhD, Dr. Roberta Jong, Serge Muller PhD, Dr. Clarisse Dromain, Dr. Maxine Jochelson, Dr. Marc Lobbes, Dr. Jordana Phillips, and many others.)

From 2013 to 2022, three other companies also gained FDA clearance of CEM systems (Hologic, Siemens, and Fujifilm). Since the first clinical use of CEM, numerous improvements to the technology have been made. In particular, the image quality of CEM has been steadily improved. A third generation of CEM technology is now available which makes the appearance (or non-appearance) of an enhancing lesion even more evident. An important step forward in the adoption of CEM was the clinical release of CEM-guided breast biopsy capability in 2021. And the latest CEM systems have also solved a problem that plagued the first generation CEM products which tended to overheat during a CEM study, which kept the system from being usable while the x-ray tube cooled off.

The clinical validation of CEM has progressed steadily and there are now hundreds of peer-reviewed studies which demonstrate the strong performance of CEM in numerous ways. CEM has gone from being considered a "poor man's breast MRI" to a modality that many consider to be superior to breast MRI because of CEM's very good specificity and superior negative predictive value (the power to correctly depict when cancer is not present). A big step forward in the clinical adoption of CEM was made in 2022 when the first ACR-BIRADS guide was published to help standardize the way radiologists report and track findings from a CEM exam. Then in 2023 the American College of Radiology (ACR) published a new guideline: "high-risk women who desire supplemental screening ... should consider contrast-enhanced mammography (CEM)." (https://www.acr.org/Media-Center/ACR-News-Releases/2023/New-ACR-Breast-Cancer-Screening-Guidelines-call-for-earlier-screening-for-high-risk-women).

CEM technology is now highly refined with excellent image quality, elimination of x-ray tube cooling delays, a very efficient and highly accurate CEM-biopsy solution, a BIRADS reporting guideline, and usage guidance from the ACR and NCCN (National Comprehensive Cancer Network). Hundreds of clinicians have now adopted CEM and use it routinely at sites across the USA and around the world. Each month additional healthcare providers launch CEM programs. CEM is now in use at every type of facility including prestigious academic medical centers, large hospital networks, rural hospitals, VA hospitals, imaging centers, and dedicated breast centers. And since most of the digital mammography and 3D mammography systems installed within the past decade can be easily field upgraded to CEM capability with the addition of new software licenses and an IV-contrast injector, the way is clear for rapid adoption of CEM by all mammography and breast imaging providers. Additional clinical trials of CEM are taking place across the USA and around the world. But many expert breast radiologists believe that CEM is already standard of care for women with dense breasts. It is only a matter of time before CEM will be offered by most mammography locations across the USA.

Bibliography

Contrast-Enhanced Mammography, Marc Lobbes, Maxine S. Jochelson, editors, Springer Cham, 2019. https://doi.org/10.1007/978-3-030-11063-5

"Contrast-enhanced Mammography: State of the Art," Radiology, Maxine S. Jochelson , Marc B. I. Lobbes, March 2, 2021. https://doi.org/10.1148/radiol.2021201948

"Contrast-enhanced Mammography: How Does It Work?", RSNA Radiographics, Wiliam F. Sensakovic, Bhavika Patel, et al., April 9, 2021. https://doi.org/10.1148/rg.2021200167

"Dual-energy contrast-enhanced digital mammography: initial clinical results of a multireader, multicase study," Breast Cancer Research, Clarisse Dromain, Fabienne Thibault, Felix Diekmann, Eva M Fallenberg, Roberta A Jong, Marcia Koomen, R Edward Hendrick, Anne Tardivon & Alicia Toledano, June 14, 2021. https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr3210

"Future Horizons in Breast Cancer Screening," Imaging Technology News, Laura Heacok, MD, November 3, 2023. https://www.itnonline.com/article/future-horizons-breast-cancer-screening

"The Next Advancement in Breast Imaging: Contrast Enhanced Mammography," Imaging Technology News, Paola Wisner, Andy Smith, PhD, Nikoe Gkanatsios, PhD, March 9, 2023. https://www.itnonline.com/article/next-advancement-breast-imaging-contrast-enhanced-mammography

"Video from RSNA 2023: Wendie Berg talks CEM with AuntMinnie.com," Aunt Minnie, Amerigo Allegretto, December 1, 2023. https://www.auntminnie.com/resources/conference/rsna/2023/article/15659424/wendie-berg-talks-cem-with-auntminniecom

"Current Insights on Breast Density, Contrast-Enhanced Mammography and Supplemental Breast Cancer Screening," Diagnostic Imaging, Jeff Hall, October 7, 2022. https://www.diagnosticimaging.com/view/current-insights-on-breast-density-contrast-enhanced-mammography-and-supplemental-breast-cancer-screening

"Current Insights and Emerging Roles for Contrast-Enhanced Mammography," Diagnostic Imaging, Jeff Hall, May 10, 2024. https://www.diagnosticimaging.com/view/current-insights-emerging-roles-contrast-enhanced-mammography?utm_source=www.diagnosticimaging.com&utm_medium=relatedContent

"Majority of women prefer CEM over MRI for supplemental screening," Aunt Minnie, Amerigo Allegretto, July 4, 2023.

https://www.auntminnie.com/clinical-news/womens-imaging/breast/article/15633774/majority-of-women-prefer-cem-over-mri-for-supplemental-screening

"Contrast Enhanced Mammography - Course Sample," ARRS, Olena Weaver, MD, July 26, 2023. https://www.youtube.com/watch?v=hcOpOWhBCFE

"Breast Cancer Screening and Diagnosis," JNCCN, September 2023, DOI: https://doi.org/10.6004/jnccn.2023.0046

"New ACR Breast Cancer Screening Guidelines call for earlier and more-intensive screening for high-risk women," ACR, May 03, 2023. https://www.acr.org/Media-Center/ACR-News-Releases/2023/New-ACR-Breast-Cancer-Screening-Guidelines-call-for-earlier-screening-for-high-risk-women

"Contrast: A Better Mammogram," Society of Breast Imaging 2021 webinar, GE HealthCare, Dr Elizabeth Morris, Dr Jason Shames, Dr Kathy Schilling, January 12, 2022. https://www.youtube.com/watch?v=77hA3wHMBlA

"Growth of a Contrast Enhanced Mammography Program in an Outpatient Setting," Hologic Inc., Julie Shisler, 2023. https://hologiced.com/wp-content/uploads/2023/06/WP-00262-Growth-of-a-CEM-Program-in-an-Outpatient-Setting.pdf

"Supplemental Cancer Screening for Women With Dense Breasts: Guidance for Health Care Professionals," Mayo Clinic Proceedings, Suneela Vegunta, MD, NCMP, FACP; Juliana M. Kling, MD, MPH, NCMP, FACP; and Bhavika K. Patel, MD; November 2021. https://doi.org/10.1016/j.mayocp.2021.06.001

"Abbreviated MR Imaging for Breast Cancer," Radiology Clinics, Laura Heacock, MS, MD, Alana A. Lewin, MD, Hildegard K. Toth, MD, Linda Moy, MD, and Beatriu Reig, MD, MPH; November 2, 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211370/

"Cancer Detection by Screening Method," DenseBreast-info., Dr Wendie Berg et al.; https://densebreast-info.org/screening-technologies/cancer-detection-by-screening-method/

Please see the "More Info About CEM" section for additional sources and references.

Published: May 10, 2024.

Patient perspective of CEM vs Breast MRI.png