1. Contrast Enhanced Mammography Andy Smith, Ph. D
Contrast Enhanced Mammography Andy Smith, Ph.D. Vice President, Image Research

2. Learning Objectives on Contrast Mammo
What it is
How it works
When to use it
Its benefits
Comparison to alternate modalities
Required hardware
Implementation challenges
Reimbursement considerations

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Terminology
Several names mean the same thing:
CEDM is Contrast Enhanced Digital Mammography
CEM is Contrast Enhanced Mammography
CESM is Contrast Enhanced Spectral Mammography
CE2D is Contrast Enhanced 2D Mammography
They are all 2D contrast images (at this time)
Throughout this presentation, acronyms will be used.
As you see, the terminology used to describe contrast enhanced 2D mammography is very similar.
CEDM is abbreviated for contrast enhanced digital mammography
CEM for contrast enhanced spectral
CESM is a term found frequently in GE SenoBright literature for contrast enhanced spectral mammography
For this presentation, we will use the term CE2D for contrast enhanced 2D mammography.
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4. Contrast Enhanced Imaging
Detection of increased formation of blood vessels (angiogenesis) associated with tumor development
Growing Tumor
The technology is designed to detect increased formation of blood vessels (angiogenesis), associated with tumor development
(Detection of increased formation of blood vessel that may be an indication of tumor development)
Increased vascularity is generally associated with tumor development. New capillary growth is triggered to provide increased supply of oxygen and food needed by cancers to thrive and grow
Cancer cells migrate to other parts of the body
Source: Time Magazine, May 1998
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5. Contrast Enhanced Imaging
Breast MRI – uses Gd contrast agent with MRI
CE2D – uses Iodine contrast agent with mammo
Same basic physiologic principle
Images lesions with higher neovascularity and extracellular leakage of contrast agent
Same basic advantages/disadvantages
High sensitivity for cancer detection
False positives: some benign lesions enhance
Both involve injection
Imaging not affected by breast density
The technology is designed to detect increased formation of blood vessels (angiogenesis), associated with tumor development
(Detection of increased formation of blood vessel that may be an indication of tumor development)
Increased vascularity is generally associated with tumor development. New capillary growth is triggered to provide increased supply of oxygen and food needed by cancers to thrive and grow

6. CE2D Potential Clinical Applications
Alternative to Breast MRI
Evaluate difficult to interpret mammograms1
Monitor effectiveness of drug therapy3
Identify potential undetected malignancies1
High risk screening (not FDA approved)
Patients contraindicated for MRI2
Contrast enhanced Digital Mammography is:
Viewed as an alternative to Breast MRI to evaluate difficult to interpret mammograms and it is less expensive than MRI
Patients contraindicated for MRI such as due to weight, phobia, pacemakers etc.
Monitor effectiveness drug therapy such as: anti-angiogenesis
Identify potential undetected malignancies* in women already diagnosed with one cancer.
1 Lewin et al. Contrast Mammography Reveals Hard-to-Find Cancers. RSNA Press Release. 30th September 2003.
2 Weinstein SP, Localio AR, Conant EF, Rosen M, Thomas KM, Schnall MD. Multimodality screening of high-risk women: a prospective cohort study. J Clin Oncol Dec 20;27(36): doi: /JCO Epub 2009 Nov 2. 3
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7. FDA approved CE systems
GE Essential SenoBright
CE2D
Hologic Dimensions I-View
CE2D + Tomo
Contrast enhanced Digital Mammography is:
Viewed as an alternative to Breast MRI to evaluate difficult to interpret mammograms and it is less expensive than MRI
Patients contraindicated for MRI such as due to weight, phobia, pacemakers etc.
Monitor effectiveness drug therapy such as: anti-angiogenesis
Identify potential undetected malignancies* in women already diagnosed with one cancer.
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8. A Typical CE2D Procedure
The following slides cover a typical procedure including contrast administration and an imaging sequence used in Hologic’s clinical trials and in published literature.
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9. 1. Contrast Agent Administration
Standard non-ionized CT contrast agent
IV injection
1.5 cc/kg body weight
3 cc/sec via Power Injector
Saline flush after injection
Need to assess for renal sufficiency
Breast is uncompressed during injection
Wait ~2 minutes post injection before imaging
This is an example of a typical contrast injection:
Step 1:
The imaging procedure requires an injection of a standard non-ionized CT contrast agent.
A typical dose is 1.5cc per kg of body weight using a power injector with an IV.
Injecting approximately 3 cc per second is injected.
during the injection the breast is not compressed
the imaging begins after a 2 minute delay after the injection
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2. Dual Energy 2D Imaging
Two exposures are made in rapid sequence:
Low kV (normal mammogram)
High kV (~45-49 kV, Cu filter)
Subtraction gives a 2D contrast image
Repeat as desired
Imaging window ends after ~6 minutes due to contrast redistribution
Let me explain the 2D imaging sequence performed by Hologic:
There are 2 exposures made in rapid sequence
The first exposure is a low kVp exposure; the technique is what is used to produce a normal mammogram
The second exposure has a higher kVp with copper filtration
The next step is to subtract the 2 images thus creating the 2D image with contrast displayed if there is contrast in the extracellular space
8 minutes is the average window for imaging due to the wash out of the injected contrast
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11. Dual-Energy Subtraction
You cannot see the contrast in high or low kV images
But you can if we subtract the images:
Subtraction = high kV - low kV
Only the low kV and subtraction images are stored
High kV
Subtraction
Low kV
In order to view the contrast after injection, 2 exposures are acquired. The subtraction image is created when the low kV image is subtracted from the high kV image. The result is an image displaying the contrast if it is absorbed within a lesion.
The Dimensions system will send only the low kV image & the subtraction image to the PACS or archive.
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CE2D – Dual Energy 2D
Low kV, High kV images acquired for each view
Views can be any order s ~
120
180
Ipsilateral Breast
Contralateral Breast
inject
240
300
480 E n e r g y
MLO CC L H
The sequence of breast and view that are acquired are decided by the hospital’s imaging protocol. Here is an example of a bilateral, two-view contrast study. In this example, the ipsilateral MLO view is acquired first. It consists of the low and high energy imaging pairs previously discussed. The breast is repositioned in the four views shown here, and dual energy pairs are taken at each breast position.
Each facility will need to determine their own CEDM protocol.
For diagnostic evaluation of an affected breast, the protocol may be to perform all the imaging on the important breast in the early phase. Views may be performed in any order.
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13. A Typical CE2D Combo Procedure
This is a typical procedure of a 2D contrast exam with the addition of a tomosynthesis scan and is used in Hologic’s clinical trials and is in published literature.
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14. CE2D + Tomosynthesis Acquisition
The CE2D images can also be part of a combo acquisition, giving 3-D tomosynthesis information
Provides co-registered physiological and morphological data
If you can correlate the CE2D lesion to a tomo lesion, can perform tomo biopsy
CE2D can also utilize tomosynthesis.
Performing the 2 images (low kV & high kV acquisition) within a combo mode acquisition, produces the tomosynthesis data along side the 2D data.
The radiologist has the to evaluate the co-registered physiological & morphological data from both the 2D & 3D images.
Compared to the contrast image alone, the co-registered image set may allow improved visibility of the radiographic margins of the lesion. From Andy
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15. 1. Contrast Agent Administration
Identical steps as in the CE2D procedure
Follow the steps as previously explained for CE2D procedure.
This is an example of a typical contrast injection:
Step 1:
The imaging procedure requires an injection of a standard non-ionized CT contrast agent.
A typical dose is 1.5cc per kg of body weight using a power injector with an IV.
Injecting approximately 3 cc per second is injected.
during the injection the breast is not compressed
the imaging begins after a 2 minute delay after the injection
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16. 2. Dual Energy 2D Combo Imaging
Three exposures are made in rapid sequence:
Low kV tomosynthesis scan
Low kV (normal mammogram)
High kV (~45-49 kV, Cu filter)
Subtraction gives a 2D contrast image
Repeat as desired
Imaging window ends after ~6 minutes due to contrast redistribution
Let me explain the Dual energy 2D combo imaging sequence performed by Hologic: there are 3 exposures made in rapid sequence
The first exposure is a low kVp exposure; the technique is what is used to produce a normal mammogram
The second exposure has a higher kVp with copper filtration
The next step is to subtract the 2 images thus creating the 2D image with contrast displayed if there is contrast in the extracellular space
~8 minutes is the average window for imaging due to redistribution of the injected contrast
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17. Combo CE2D – Dual Energy 2D with Tomosynthesis
Tomo, Low kV, High kV images acquired for each view
Views can be any order
If the procedure is performed with tomosynthesis acquisition, within the combo mode, the tomosynthesis scan is acquired first (click) and then the 2D images; both the low kV & high kV images.
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Patient Work Flow
From Palmieri et al, 2016 ARRS Annual Meeting
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Example Images
Courtesy of Andrea Woodroof, Kentucky Breast Care
I will share 4 example cases with you. These studies were provided by the following:
John Lewin, MD, Denver, CO
Kaohsiung Veterans General Hospital, Taiwan
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Case 1
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21. CE2D for Discordant Findings
52 y.o. female, presented for screening
0.8 cm spiculated mass in the left axillary tail noted on both 2D and 3D
Focal area of possible distortion noted on 3D
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22. CE2D for Discordant Findings
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23. CE2D for Discordant Findings
Area of distortion couldn’t definitively be correlated on ultrasound for US biopsy
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24. CE2D for Discordant Findings
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25. CE2D for Discordant Findings
Area of distortion couldn’t definitively be correlated on ultrasound for US biopsy
The enhancing mass on CE2D was correlated with the tomo distortion
Tomo-guided biopsy ensued
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26. CE2D for Discordant Findings
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Case 2
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28. CE2D for MRI Contraindications
Patients with pacemakers
Body habitus
Claustrophobia
Lack of insurance or deductible cost issues
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29. CE2D for MRI Contraindications
50 y.o. female with pacemaker and 6-month history of irritation underlying skin of left breast
Patient assumed irritation due to the pacemaker, but it didn’t resolve
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30. CE2D for MRI Contraindications
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31. CE2D for MRI Contraindications
Imaging demonstrated 4 cm spiculated mass
US biopsy
Pathology: Invasive ductal carcinoma
Patient referred to oncology and neoadjuvant chemotherapy
Pre and post-treatment MRI not possible; PET declined by insurance
CE2D performed
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32. CE2D for MRI Contraindications
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33. CE2D for MRI Contraindications
Prior to therapy, 3.4 cm mass showed strong enhancement
3 month interval showed decrease of size of mass to 1.7 cm.
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34. CE2D for MRI Contraindications
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Case 3
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Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
49 y.o. female with palpable mass
2D/Tomo imaging revealed spiculated mass
Pathology IDC
Extent of disease difficult to measure with either 2D or Tomo due to dense parenchymal tissue
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Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
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Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
Prior to initiation of neoadjuvant chemotherapy, CE2D was performed
1.5 x 1.3 cm enhancing spiculated mass
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Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
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Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
Prior to initiation of neoadjuvant chemotherapy, CE2D was performed
1.5 x 1.3 cm enhancing spiculated mass
CE2D image after 3 months demonstrates partial response to chemotherapy
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Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
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Clinical Performance
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Clinical Performance
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44. Diagnostic Clinical Performance
CE2D higher sensitivity than 2D or tomo
CE2D and bMRI show comparable performance
CE2D and bRMI have comparable accuracy in tumor sizing
Patients prefer CE2D over bMRI
In summary, CE2D
Alternative to Breast MRI
Evaluate difficult to interpret mammograms
Patients contraindicated for MRI
Monitor effectiveness of drug therapy
Identify potential undetected malignancies*
Fallenberg E, Dromain C, Diekmann F, et al. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size, Eur. Radiol. 24 (1) (2013) 256–264.
Chou C, Lewin J, Chiang C et al. "Clinical Evaluation of Contrast-Enhanced Digital Mammography and Contrast Enhanced Tomosynthesis-Comparison to Contrast-Enhanced Breast MRI" Eur J Radiol Dec; 84(12): [Epub 2015 Oct 1].
ochelson M, Dershaw D, Sung J, et al., Bilateral contrast-enhanced dual-energy digital mammography: feasibility and comparison with conventional digital mammography and MR imaging in women with known breast carcinoma, Radiology 266 (3) (2013) 743–751.
Lobbes MB, Lalji UC, Nelemans PJ, et al. The quality of tumor size assessment by contrast-enhanced spectral mammography and the benefit of additional breast MRI. J Cancer. 2015;6(2):
Hobbes M, Taylor D, Buzynski S et al. “Contrast-enhanced spectral mammography (CESM) and contrast enhanced MRI (CEMRI): Patient preference and tolerance” J Med Imaging Radiat Oncol Jun;59(3): [Epub 2015 Apr 21].
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Comparison to MRI
Advantages of CE2D
Lower cost procedure
Faster procedure (7-10 min vs min for bMRI)
Fast readings
Good imaging of microcalcifications (low energy image)
Disadvantages of CE2D
Don’t get both breasts at same time
Hard to get time-activity information
Involves radiation, but FFDM usually ordered with bMRI
Iodine contrast agent adverse reactions
In summary, CE2D
Alternative to Breast MRI
Evaluate difficult to interpret mammograms
Patients contraindicated for MRI
Monitor effectiveness of drug therapy
Identify potential undetected malignancies*
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Required Hardware
Mainly a software upgrade
Also includes additional x-ray filter (copper)
May require detector upgrade for older systems
In summary, CE2D
Alternative to Breast MRI
Evaluate difficult to interpret mammograms
Patients contraindicated for MRI
Monitor effectiveness of drug therapy
Identify potential undetected malignancies*
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47. Implementation Considerations
Power injector
Who will place the IV line and perform injection?
Crash cart
Review risk mitigation policies regarding contrast agents
Menstruation cycle. Same as MRI days after last period
Tube heating. Need to wait ~10 minutes after procedure
In summary, CE2D
Alternative to Breast MRI
Evaluate difficult to interpret mammograms
Patients contraindicated for MRI
Monitor effectiveness of drug therapy
Identify potential undetected malignancies*
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Reimbursement
In summary, CE2D
Alternative to Breast MRI
Evaluate difficult to interpret mammograms
Patients contraindicated for MRI
Monitor effectiveness of drug therapy
Identify potential undetected malignancies*
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Summary
Potential Clinical Applications
Viable alternative to MRI
Evaluating patients contraindicated for MRI
Monitoring effectiveness of drug therapy
Identify potential undetected malignancies
In summary, CE2D
Alternative to Breast MRI
Evaluate difficult to interpret mammograms
Patients contraindicated for MRI
Monitor effectiveness of drug therapy
Identify potential undetected malignancies*
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50. Thank you! Email: andrew.smith@hologic.com