1. Contrast Enhanced 2D Mammography
This presentation is a description of the theory of contrast enhanced 2D mammographic imaging.
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2. Agenda Definition of contrast enhanced digital mammography
The importance in identifying breast cancer
An understanding of the 2D procedure: contrast agent and imaging sequence
Sharing of example cases
It will include
Definition of Contrast enhanced digital 2D mammography
The importance of this modality in identifying breast cancer
An understanding of the 2D procedure: contrast agent and imaging sequence
Sharing of example cases
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

3. 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
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 2D Mammography (CE2D)
Detection of increased formation of blood vessels (angiogenesis) associated with tumor development
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
Source:
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5. Potential Clinical Applications
Alternative to Breast MRI
Evaluate difficult to interpret mammograms1
Patients contraindicated for MRI2
Monitor effectiveness of drug therapy3
Identify potential undetected malignancies1
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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6. Regulatory Status Product FDA Clearance CE Mark Hologic CE2D GE
SenoBright
Currently, commercially available approvals have been obtained by Hologic & GE
The FDA approval stated the indications for use: This imaging technique can be used as an adjunct following mammography and/or ultrasound exams to localize a known or suspected lesion.
This imaging technique can be used as an adjunct following mammography and/or ultrasound exams to localize a known or suspected lesion
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

7. 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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8. 1. Contrast Agent Administration
Standard non-ionized CT contrast agent
IV injection
1.5 cc/kg body weight
3 cc/sec via Power Injector
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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9. 2. Dual Energy 2D Imaging Two exposures are made in rapid sequence:
Low kV (normal mammogram)
High kV (~45-49 kVp, Cu filter)
Subtraction gives a 2D contrast image
Repeat as desired
Imaging window ends after ~8 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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10. 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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11. 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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12. A Typical CE2D Combo Mode 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.
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

13. CE2D + Combo Mode Procedure
The CE2D images can also be part of a combo mode acquisition, giving 2D + 3D™ exam information
Provides co-registered physiological and morphological data
Compared to the contrast image alone, the co-registered image set may allow improved visibility of the radiographic margins of the lesion
If you can correlate the CE2D lesion to a tomo lesion, a 3D™ guided biopsy can be performed
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 & tomo slices.
Compared to the contrast image alone, the co-registered image set may allow improved visibility of the radiographic margins of the lesion. If you can correlate the CE2D lesion to a tomo lesion, a tomo guided biopsy can be performed
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

14. 1. Contrast Agent Administration
Follow the steps as previously explained for 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
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

15. 2. Dual Energy 2D Combo Mode Imaging
Three exposures are made in rapid sequence:
Low kV tomosynthesis scan
Low kV (normal mammogram)
High kV (~45-49 kVp, Cu filter)
Subtraction gives a 2D contrast image
Repeat as desired
Imaging window ends after ~8 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
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

16. Combo Mode CE2D: Dual Energy 2D + 3D™ scan
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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17. Example Images Courtesy of Andrea Woodroof, MD Kentucky Breast Care
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18. Case 1 CE2D procedure for Discordant Findings
52 year old female, presented for screening
0.8 cm spiculated mass in the left axillary tail noted on both 2D and tomo slice
Focal area of possible distortion noted on tomo slice
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19. CE2D for Discordant Findings
Using CE2D to resolve discordant findings
Left breast – 2 areas found on tomo
Screening exam –0.8 cm spiculated mass in left axillary tail noted on both 2D and 3D
Focal area of possible distortion noted on 3D
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20. CE2D for Discordant Findings
Area of distortion could not definitively be correlated on ultrasound for ultrasound guided biopsy
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21. CE2D for Discordant Findings
Couldn’t be definitively correlated on U/S for biopsy
Mass enhanced on CE2D and distortion localized with tomo
Tomo guided biopsy ensued
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22. CE2D for Discordant Findings
Area of distortion could not definitively be correlated on ultrasound for U/S biopsy
The enhancing mass on CE2D was correlated with the tomo distortion
3D™ guided biopsy ensued
Mass enhanced on CE2D and distortion localized with tomo
Tomo guided biopsy ensued
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23. CE2D for Discordant Findings
Mass enhanced on CE2D and distortion localized with tomo
Tomo guided biopsy ensued
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24. Case 2 CE2D procedure for MRI Contraindications
Patients with pacemakers
Body habitus
Claustrophobia
Lack of insurance or deductible cost issues
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25. CE2D for MRI Contraindications
50 year old female with pacemaker and month history of irritation underlying skin of left breast
Patient assumed irritation due to the pacemaker, but the skin irritation did not resolve
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26. CE2D for MRI Contraindications
Using CE2D for MRI-contraindicated patients
Patient had 2D/3D exam revealing a 4 cm spiculated mass in the left breast
U/S guided bioposy: IDC
CE2D performed before & after neoadjuvant therapy –
Prior to neoadjuvant therapy showed 3.4 x 3.4 mass in LMLO view
Following neoadjuvant therapy, CE2D shows an interval decrease in size of mass to 1.7 x 1.7 cm
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27. CE2D for MRI Contraindications
Imaging demonstrated 4 cm spiculated mass
U/S guided biopsy
Pathology: Invasive ductal carcinoma
Patient referred to oncology and neoadjuvant chemotherapy
Pre and post-treatment MRI not possible
PET scan declined by insurance
CE2D exam performed
U/S guided bioposy: IDC
CE2D performed before & after neoadjuvant therapy –
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28. CE2D for MRI Contraindications
U/S guided bioposy: IDC
CE2D performed before & after neoadjuvant therapy –
Prior to neoadjuvant therapy showed 3.4 x 3.4 mass in LMLO view
Following neoadjuvant therapy, CE2D shows an interval decrease in size of mass to 1.7 x 1.7 cm
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29. 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.
Prior to neoadjuvant therapy showed 3.4 x 3.4 mass in LMLO view
Following neoadjuvant therapy, CE2D shows an interval decrease in size of mass to 1.7 x 1.7 cm
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30. CE2D for MRI Contraindications
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31. Case 3 Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
49 year old female with palpable mass
2D/3D imaging revealed spiculated mass
Pathology: Invasive Ductal Carcinoma
Extent of disease difficult to measure with either 2D or tomosynthesis imaging due to dense parenchymal tissue
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32. Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
CE2D for measuring extent of disease in very dense breasts and for evaluation of response to therapy
2D/tomo exam for palpable mass revealed spiculated mass in dense tissue
U/S biopsy: IDC
CE2D imaging prior to and after neoadjuvant therapy demonstrated an interval decrease in the size of the mass
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33. Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
Prior to initiation of neoadjuvant chemotherapy, CE2D exam was performed
1.5 x 1.3 cm enhancing spiculated mass
CE2D for measuring extent of disease in very dense breasts and for evaluation of response to therapy
2D/3D exam for palpable mass revealed spiculated mass in dense tissue
U/S biopsy: IDC
CE2D imaging prior to and after neoadjuvant therapy demonstrated an interval decrease in the size of the mass
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

34. Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

35. Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
Prior to initiation of neoadjuvant chemotherapy, CE2D exam was performed
1.5 x 1.3 cm enhancing spiculated mass
CE2D exam after 3 months, demonstrates partial response to chemotherapy
CE2D for measuring extent of disease in very dense breasts and for evaluation of response to therapy
2D/3D exam for palpable mass revealed spiculated mass in dense tissue
U/S biopsy: IDC
CE2D imaging prior to and after neoadjuvant therapy demonstrated an interval decrease in the size of the mass
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

36. Evaluating Extent of Disease in Dense Breasts and Neoadjuvant Chemotherapy Response
CE2D for measuring extent of disease in very dense breasts and for evaluation of response to therapy
2D/3D exam for palpable mass revealed spiculated mass in dense tissue
U/S biopsy: IDC
CE2D imaging prior to and after neoadjuvant therapy demonstrated an interval decrease in the size of the mass
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472

37. Future Directions* Contrast-guided biopsy Tomo contrast mammography
both 2D (stereo) and 3D™ guided procedures
Tomo contrast mammography
* Not commercially available
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38. Clinical Performance
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39. 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
Hologic Proprietary - For Educational Purposes Only - November rev004 PRE-00472