Welcome to Noon Conference hosted by NLINE. Noon Conference connects the global radiology community through free live educational webinars that are accessible for all and is an opportunity to learn alongside top radiologists from around the world. We encourage you to ask questions and share ideas to help the community learn and grow. You can access a recording of today's conference and previous Noon Conferences by creating a free MRI online account. Today, we're honored to welcome Dr. Jordanna Phillips for a lecture on Contrast Enhanced Memography, Time for Implementation. Dr. Phillips is Chief of Breast Imaging at Boston Medical Center and Associate Professor of Radiology at Boston University. She's an expert in Contrast Enhanced Memography, performing research on the topic as well as lecturing nationally on implementation strategies. At the end of the lecture, please join her in a Q&A session where she will address questions you may have on today's topic. Please remember to use the Q&A feature to submit your questions so we can get to as many as we can before our time is up. With that, we're ready to begin today's lecture. Dr. Phillips, please take it from here. Thank you.  So, I am so thrilled to be here with everybody today talking about Contrast Enhanced Memography. It's a topic that I find incredibly exciting for our field and hopefully all of you will too. I know there have been a lot of questions about it. It's kind of becoming a hot topic. People are implementing it. So, feel free after the lecture is over if we don't have enough time for questions to reach out to me. I'm happy to answer anything. So, let's get started. These are my disclosures. So, this is what we're going to be talking about today. We'll start with the basics, move on to some of the challenges of Contrast Enhanced Memography. As we know, there's always some difficulty when you're starting something new. We'll talk about how people are using it in clinical practice, and then we'll move on to where it's headed in the future and some other kind of key ideas to mention. So, we're going to start by talking about the basics. The wonderful thing about Contrast Enhanced Memography, and I should start by saying you'll notice at the top of the slide it's a C-E-N, Contrast Enhanced Memography. Some people use the word Contrast Enhanced Spectral Memography or C-E-S-N or Contrast Enhanced Digital Memography or C-E-D-N. These are all the same thing. So, I use C-E-M, so you'll see that throughout the talk. So, the wonderful thing about Contrast Enhanced Memography is that it's just an adaptation of what we already know, which is conventional 2D mammography, which are the standard four views, but there are two key differences with a Contrast mammogram. The first difference is that the images are acquired entirely after the injection of iodinated contrast. So, a patient comes into the department, they have an IV line place, which is a difference that the patient notes. Through the IV line, they have the iodinated contrast administered. Two minutes from the start of the injection, they have what they perceive to be their normal mammogram. But this is where the second difference comes into play. This mammogram is actually performed using a dual energy technique. And so, what does this mean? Well, for every imaging position, every time the breast is compressed in the C-C or the MLO view, the unit is actually acquiring two pictures. The first picture is a low-energy image, which looks just like a conventional 2D mammogram. You can see it here. Studies have actually shown that it's really similar, no different non-inferior to a conventional 2D mammogram, which is great. You'll notice on the low-energy image that there's already contrast in the breast, but you cannot see it on this 2D image, on the low-energy image. And that's because this low-energy image is performed below the cage of iodine, so it doesn't capture any of that iodine that's in the breast. The second image that's acquired is a high-energy image. You'll notice it's blued out on my screen. And that's because it's non-interpretable. This high-energy image is performed above the cage of iodine, so it captures all of that contrast material that's in the breast, but we don't ever see this picture. The unit automatically post-processes the low-energy and the high-energy images together to create something called a recombine image. And this image is similar to a subtraction image on MRI where it really just highlights. It showed really well those areas of contrast enhancement. The low-energy image and the recombine images are what we see as radiologists. Those are the images that get sent to our workstation for imaging review. So what's excellent about contrast enhancementography is that we get to combine what we know, which is information on morphology and density, and we get to combine that with information on enhancement and we don't need an MRI to do it. It's all performed at the same time. This imaging modality, contrast enhancementography, was actually approved over a decade ago at this point. It was approved for use in the diagnostic setting in 2011. It's only really increased throughout the country in the past few years. So let me show you an example of a contrast mammogram. This was a 55-year-old woman who had a mass on her screening and she was recalled and she had a diagnostic contrast enhanced mammogram. These are her low-energy images. Again, they look just like a 2D mammogram. Remember that the iodinated contrast has already been administered. There is already contrast within the breast. We just don't see it. So these are the low-energy images and you can see that there's a mass in the right breast. Can't really appreciate its margins that well. But then look at the recombined images. These are the images that show the enhancement and you can see that there's definitely a mass here. You can see the margins of the mass. You can see how the mass is taking up that contrast to teterogeneous, necrotic in the center. And what you'll also notice is that there's no enhancement throughout the remaining aspect of that breast. So not only does it help us better classify what we're seeing, better understand it, or characterize it, I should say. It also helps exclude cancer in other portions of the breast. This is really great. This was a triple negative breast cancer. So this is how contrast mammogram is acquired. So again, we start with an injection. Ivy line goes in the arm. We inject iodinated contrast material at a dose of 1.5 cc per kilogram and at a rate of 3 cc per second through a power injector. Two minutes from the start of the injection, we start acquiring standard for images of a mammogram. You'll see here each imaging set, so the low energy and the high energy image are considered an imaging set. Each of these is actually acquired one minute apart, such that the total exam takes roughly five to six minutes. If you're going to perform additional images, which sometimes I do, for example, I acquire 90 degree laterals for my diagnostic exams, those happen after the standard four views. And they have to happen within 10 minutes because we want to make sure that whatever contrast is in the breast, we can see it and it hasn't washed out. What's important to remember after the images are acquired, they get sent to our workstation, as I mentioned before, is that a contrast mammogram includes interpretation of both the low energy and the recombined images. They are both a part of it. So even if you see a suspicious abnormality on the low energy images, right, calcifications, and there's no enhancement, that is still considered a positive contrast enhanced mammogram. And there was actually a meta-analysis that was done that looked at data on contrast enhanced mammogram and found that when both the low energy and the recombined images are included in the interpretation, the sensitivity is 95% and the specificity is 81%, which is fairly high. So it's really important to remember that both are included in your interpretation. But let's get into a little bit more about the difference between contrast enhanced mammography versus conventional mammogram. There are some obvious benefits. To start, we can see cancers that would otherwise be obscured by glandular tissue on a mammogram. Let me show you an example or another example of this. This was a patient who had an asymmetry in the central portion of her left breast. You can see it's marked here by the circle. She came back for a diagnostic contrast mammogram.  And you can see the mass there in the central aspect of the breast. The question is, is it a mass? Is it an asymmetry? On the low energy images, it really looks like a discrete finding. When we do the recombined images, we can see that there is definitely an abnormality there. This is a true finding. And we can also see that it's limited to that portion of the breast. And there are no other suspicious areas of enhancement throughout the remaining aspect of that breast. So again, helps us characterize allusion and also improves our understanding of if there are other abnormalities throughout the remaining aspect of that breast or the contralateral breast. Studies are consistent. I'm not even going to show you one specific study on this, but the studies are consistent in that contrast-enhanced mammography performs better than MAMO for all performance metrics. And this isn't surprising because it's kind of like had where it's just taking the information that we already have and providing more information. So we still have our conventional 2D images. We're just providing more information, which is the enhancement, to help us identify more cancers and to help us exclude things that are just superimposed breast tissue. Another nice characteristic of this exam is that it can be performed at the same time as the diagnostic appointment. So you'll see, I already mentioned that if I have an abnormality that I identify on screening, I can bring the patient back and do a diagnostic contrast-enhanced mammography and write them. I can better evaluate the finding and I can actually use it as a staging exam. I can see the full extent. I can see if there are other areas to worry about. And I could do it all at the time of the diagnostic appointment. I can show the patient the imaging findings. It's also, when compared to mammography, it's a timed exam and it's relatively fast. So we looked, our group looked, at how long it actually takes to do a contrast mammogram. How it compares to diagnostic mammography, you'll see the DM is for diagnostic mammography. So we can figure out how much time we need to schedule or a lot for this exam. So we compared these two. We also compared it to CT and MR, but I'm not going to focus on those. And we looked at different elements of the exam. We looked at EST, which is getting the equipment set up. PST, which is getting the patient set up. ET is exam time and PT is the post-exam time. And what you see when you look at all these times taken together is that the contrast mammogram was roughly 30 minutes longer than a diagnostic exam. But when we broke that down, we actually found that the reason for the increase in length is because of that equipment setup time and patient setup time. And that the actual time for the exam, because it's a timed exam, was actually exceptionally similar. So what that told us is that, as you would expect, if we use the MAMO room to put in the IV line and to talk to the patient ahead of time, it's going to extend the time of the contrast-enhanced MAMO exam. What's better to do is to actually be able to do all of those preparatory steps in another room so that you're only using the MAMO room for the time of the exact, the actual exam, which would be similar to a diagnostic exam. Another benefit is that you don't need a whole new machine or unit. It's not like MRI where you have to get the whole, your whole, the whole room out, outfitted for this specific modality. This is just, if you have a MAMO unit that's capable of being upgraded to allow for dual energy, you can, you take the machine out of use for about a day or two. You have some software firmware upgrade. You have to add in a new filter to allow for the high energy images. This is a picture of a copper filter. Also titanium filters can be used. But this is really a simple thing to allow you to get these, this added information. Last thing I'm going to mention about radiation dose. So radiation dose is really a tough topic because we all try to compare radiation dose across modalities, across vendors. And it's very difficult to do because all of the vendors acquire images in a different way. And so it's very hard to compare one to another to say there's more or there's less. So what we did to get a sense for the actual radiation dose of contrast MAMO is we took about 40 plus patients in our practice who had imaging on all of the different vendors that we have and they had all different types of images. 2D, 2D plus DBT. And we compared the radiation dose. We calibrated all of it and compared the radiation dose across all of these exam types. And we stratified our results by breast tissue thickness. And what we found is that one of the exams that we perform all the time, which was a 2D plus a DBT for screening, we found that that was the highest radiation dose across breast tissue thicknesses, that that blue arrow still well within the range. So I don't want to suggest that this is too high of a dose, but just this is what it was. A second vendor, which was these were the 2D images only, had the lowest radiation dose across breast tissue thicknesses. And this is where contrast MAMO fell. So contrast MAMO was actually the dose of one of these exams which include low energy and recombined, I'm sorry, low energy and high energy images was actually similar to, was within the range of what we were providing to patients on a daily basis. So from my perspective, the take home for radiation dose, it's not that it's higher or lower than a different exam, but that it's well within the range of what we're doing for women every day. But we get this added information on enhancement, which we are not getting from our tests that only provide morphologic and density information. So let's talk about contrast enhanced MAMO compared to MRI. Well, there is, the studies have shown a similar accuracy of contrast MAMO to MR. What this means really, it's a measure of how well contrast MAMO accuracy is a measure of how well it finds cancer and how well it doesn't find non-cancer. So let's look at that sensitivity is ability to find cancer. These are two meta-analyses performed in 2020 and 2022 with a different number of included studies. And they found that, the first study found that the sensitivity for contrast MAMO and MRI was the same 97%. And the second one, more recent one found that there was a difference in sensitivity. Contrast MAMO had a sensitivity of 91%. MRI had a sensitivity of 97%, which was a little bit different and actually not unexpected. Given that MRI is a cross-sectional imaging exam, we're getting much more information than we can on contrast enhanced MAMO, which is a 2D planar exam. But when we look at the specificity, we see that the specificity is actually higher for contrast enhanced MAMO as compared to MRI. And this again, really the take home message that I would say a majority of us, we when looking at all of the individual studies and at these meta analyses is that MRI does do a little bit of a better job at finding individual breast cancers and by really a few extra, but it has a much, contrast enhanced MAMO has a much better specificity. So that overall the diagnostic accuracy of these two exams is fairly comparable. We'll get into the specific clinical, how we're using it in clinical practice and how the data compares. Let's look at an example of a contrast enhanced MAMO grant compared to MRI. So this is a low energy image from a contrast MAMO, we see a mass. These are the recombined images where we see a mass, but we can also see enhancement extending towards the nipple. And so let me show you, this is the MRI exam, which shows the exact same finals. And I would say for people that are new to contrast MAMO, whenever you look at the recombined images, often enough, if you were to then perform an MRI, the images are almost identical. Identical, maybe as strong. They're very similar. And so how you would describe the imaging finding on the recombined images is similar to how you would describe it on an MRI. Contrast enhanced mammography is also more affordable at an MRI. We bill it as a diagnostic mammogram plus contrast. There's no formal code for it yet. It's also more accessible. As I mentioned, it's just an add-on to a mammography unit that can be upgraded. It allows for real-time interpretation, as I also mentioned. And so often enough, MRI is read offline. We read them when the patients are not here. For contrast enhanced mammography, we can read them while the patient is sitting in our department. The number of times that I've done these exams and have shown the patients the images have shown them when they're totally negative. And a patient with dense breast tissue is really comforting to these women to know, no, no, they can believe these results. Or similarly, in a patient where the contrast mammoth is done for staging, I can say, no, no, don't worry. This area is isolated to this one small thing. You're good. The rest of your breasts are just fine. So this imaging modality allows us to maintain that communication with our patients, especially in this time where I think that that communication and connection is important. Patients also prefer contrast enhanced mammoth. This was a study that we recently published. These are women who have a history of breast cancer and we asked them, if those MRI and contrast mammoth have an equal chance of finding your breast cancer, which would you prefer? And you can see that a far majority, 73% hopefully, like my annotations, actually would prefer CEM, only 10% preferred MRI. Another nice thing is that we don't have to do an MRI biopsy. So for anybody considering CEM, I would highly recommend that you get CEM biopsy. I have not done it myself, but I've seen them and they are awesome. CEM biopsy is just like a stereobiopsy. The patient experience is very similar and at least what I have perceived is so much better than what women are going through for these MRI biopsies. So it allows us to divert patients from MRI biopsy to CEM biopsy and that's, I think, an absolute game changer for this imaging modality. We're going to move on to talking about challenges of CEM as I mentioned. You know, whenever we, we always have to talk about the challenges. There's always something that we need to discuss. And the main challenge of contrast enhancement really relates to contrast administration, as you would expect. So there is a real risk of contrast-related events. This includes what we used to call contrast-induced nephropathy and now it's called contrast-associated or contrast-induced acute kidney injury. And it also includes extravization of the contrast material in the arm after it's administered through the IV line. And contrast-associated acute kidney injury or contrast-induced nephropathy is not really, it's not really a thing anymore. Or I should say people are questioning whether it's really a thing anymore. And so some institutions are actually not even evaluating for underlying risk factors for contrast, for this contrast complication. That being said, the ACR contrast manual still, still treats it as an entity to be mindful of. And so you should talk to your individual institution to see how they navigate this. Do they test people's renal function before doing, before administering contrast? Or you can always, you can always refer to the ACR contrast manual for how to navigate this. There's also a challenge of contrast administration on workflow. Again, we have to place an IV line. We have to screen patients to make sure they're not going to, they're not at increased risk for developing a contrast reaction. And so that can impact the workflow through the department. Another challenge of contrast are false positives. So similar to MRI, areas that are benign can take up the contrast material. That's a challenge. Contrast nephropathy, when we look at it at the moment, it's really just, is there a contrast or is there no contrast? We don't have all of the information that we have with MRI, you know, T2 signal and maybe even diffusion weighted sequences. And so there's the real possibility to just see abnormal enhancement and to say, oh, this is concerning for breast cancer and we have to do something about it. So there are false positives. Let's look at an example of that. This was a 56 year old woman who had a history of left breast cancer that was treated with wide excision alone. And she had new right breast calcification. So you can see there's the surgical bed on the left, I marked it. That was where the wide excision was done. And these are the new calcifications on the right. These are, this is the image showing, you know, highly pleomorphic, linear branching calcifications by Reds 5. So we are worried about these for sure. These are the recombined images that show that there's abnormal enhancement associated with the new calcifications, not surprising because these were concerning.  But what you'll also notice is that there's mass enhancement in the surgical bed. And we saw this and we thought, for sure this is going to be a recurrence. This patient didn't have radiation therapy. It was only wide excision. And so we thought this was going to be a recurrence. We ended up having an MRI because this was early on in our implementation. We can see the same thing on the right with those calcifications. We had enhancement. And we also saw mass enhancement in the surgical bed on the left. And it turned out that this was not recurrence because we did a biopsy. And we found that it was just post treatment change in the area of fat necrosis. So this is an example of a false positive on contrast mammogram and MRI. Another challenge of contrast mammogram are false negatives. False negatives happen because you have to remember that a contrast mammogram is still just a mammogram. We're still limited by what you can get on the detector. So sometimes you can miss lesions that are in the deep chest wall or in the medial breast or certainly not imaging the axilla but that's not really the goal. Another reason for a false negative has to do with PPE which is background prankable enhancement. So we know from MRI that normal glandular tissue can take up contrast to varying degrees. Same thing happens on a contrast mammogram and you can see the image all the way on the left is minimal background prankable enhancement where there's almost no uptake of the contrast material as compared with Mark background prankable enhancement which is quite a bit of contrast uptake. So we have the same four categories on contrast mammograms we do with MRI minimal mild moderate and marked and you can imagine that when you have marked a lot of background prankable enhancement it might be difficult to appreciate a solitary area of enhancing and so this can be a reason for a false negative on contrast enhancement monitoring. Another challenge of contrast mammogram and this is really more of an implementation challenge has to do with recombined only findings. We know from the literature that even if you see an abnormality on recombined imaging only even if it's only one view you have to take these seriously. One of the studies that was put out by Kim and colleagues showed that BOSI non-mass enhancement and mass enhancement had positive predictive values of at least 6% all the way up to 40% so you have to address these if you see them and why that's an implementation challenge is that what happens what do you do in these circumstances? The first thing you do is you have to identify see if there's a low energy correlate because then maybe you can do a stereo or a tomosynthesis guided biopsy. Well if you don't have that you can do an ultrasound and see if you have a target for ultrasound guided core biopsy but if you don't have that then what do you do? So we used to send these patients to MRI to do an MRI biopsy now with contrast enhanced mammogram biopsy you can do that but you have to know how you're going to navigate these findings want to implement contrast enhanced mammogram because it's a real thing it'll come up and you have to address it the same at the very least you would do a follow-up which is not recommended so this is like the whirlwind tour of contrast enhanced mammogram biopsy we're going to move on to CEM and clinical practice let's start here so there are a variety of clinical indications for contrast enhanced mammogram biopsy these are all diagnostic indications as you'll notice because I mentioned it's only approved in the diagnostic setting and the last one on this list is higher supplemental screening and that's because there are new recommendations that are allowing us to do contrast enhanced mammogram in this setting but it is not FDA approved or at least allowing us I should say recommending as an alternative to MRI and I'll get into that for this talk we're going to focus on these first three indications cancer staging evaluate neoadjuvant chemotherapy response and recall from screening so this is the first case finally some pictures this is a 68-year-old woman who is recalled for right breast architectural distortion I'm not going to show you the TOMO images you can see the distortion is here marked by the yellow arrow when we do the recombine images you can see that there is a discrete mass here and so this this contrast mammogram allowed us to both characterize the finding and also delineate extent and that's really one of the beautiful things about this imaging modality it allows us to do both right at the time of the diagnostic exam you can also do this after biopsy so this was a grade two hormone receptor positive breast cancer this is another case this is a 68-year-old woman who was recalled again for right breast architectural distortion this is the area of distortion it was a very subtle finding not even worth showing you the 2D images for this particular case these were the recombine images that showed us for sure that there's an abnormality in this location but it also showed us that there were other abnormalities located in both breasts these were all malignant so this is an example for sure for architectural distortion it helps us say is this area something to worry about or not and is there additional disease in other parts of the breast we had an MRI again because this was during the earlier parts of our implementation and you can see that these findings showed up on the MRI as well and they were all malignant so again this really just highlights how similar the images are that we see on those recombined images to our MRI images which is really why the sensitivities of the exam is so similar this is another exam but we've talked about distortion so far this is a mass this is a 75-year-old woman who had a history of bilateral breast cancer and recalled for diagnostic CM for this right breast mass now this what I like about this case we can all see the mass it's marked by the yellow arrow but what I liked about this case and why I'm showing it is because we know that once you have cancer treatment it can distort the breast it can be difficult to figure out what is just related to the surgery and what is new that we need to worry about and remove or treat and so what the recombined images did for us is they just showed us where the cancer was and all of those other areas of distortion related to the post-surgical changes just disappear and this was a grade 3 hormone receptor positive cancer this is another example of contrast mammogram this was DCIS this is for calcifications and calcifications are different than distortion mass and we'll talk about that this was a patient of DCIS you can see it was already biopsy that was the clip these are the calcifications linear branching very very suspicious right not surprising this came back as DCIS this person couldn't get an MRI for a disease extent so we did a contrast mammogram and what you'll notice is that the recombined images show no enhancement so this is an example and the reason I include I'm including it this is an example still of a positive contrast mammal because it's showing those calcifications even though it's positive even though there's no enhancement here and this is one of the challenge of contrast mammal for calcifications where some DCIS low grade invasive doctoral cancers might not show enhancement we have to act on it anyway so I'm thinking about cancer staging for calcifications we don't actually use the recombined images to help us determine whether to do something about the calcifications it's really to see is there enhancement separate or beyond the area of calcifications that might impact the overall treatment plan so in summary here are a few studies that I'm just pulling out from the literature some can now in 2019 they compared CEM to MRI for cancer staging and they found that the sensitivities for the primary cancer site are 93% versus 91 and if you were to look through the literature you would see this over and over again these sensitivities being very similar to each other and they also found that both imaging modality CEM and MRI overestimate the tumor size to a similar degree and this overestimation is by a few millimeters we are not talking about centimeters here low base et al more recently we're looking at contrast enhanced mammography and MRI and it's their evaluation of ILC which is invasive lobular cancer we found that both of them overestimated ILC by around two millimeters very similar and then Lee and colleagues in 2021 providing information not on how well they found the cancer but on what the positive predictive value which is really how well when you see something on contrast mammary MRI is it likely to bake cancer and you'll see that the positive predictive value is much higher for CEM over MRI and this again is kind of borne out over and over again which is when you see an abnormality on contrast mammary it is more likely to be breast cancer than when you see an abnormality on MRI and this likely is because again it's a 2D it's a planar projection so if it becomes obvious enough for us to see it then we should act on it to a greater extent than with MRI and yeah that's the main that's made me what I have to say about that so in general though the take on point is that contrast enhanced mammography can be used as an alternative to MRI so forgetting you know the data is there and this is what you should remember so now we're going to look at a different area a different clinical indication which is using contrast enhanced mammography to evaluate for neobagin chemotherapy so this was a patient who had a grade three her two positive breast cancer and had a positive lymph node you can see the cancer marked by the thicker arrow and the node marked by the longer thinner arrow and so this is an example where the contrast mammary was used to see how the patient responded to treatment so these are the recombined images initially before treatment which show you what you would expect the cancer and the node and this is what we see after treatment so the image in yellow are the pretreatment images and the images with the white annotations are post treatment and so on our low energy images we can see that it looks like there's improvement but you probably remember from other talks on neobagin therapy where typically we categorize things as total response no response and a partial response which has to be at least 30% and so the question is where does this fall in is this a partial response is this a total response so we get our recombined images which give us a much better sense as to how this patient has responded to the chemotherapy treatment so there was a meta analysis in 2023 so recent that showed that the sensitivity for evaluating neobagin chemotherapy treatment response was actually better for CEM over MRI and it showed that the specificity was actually a little bit worse 68% to MRI but they're always kind of balancing you know these two imaging exams are always kind of teetering like one is a little bit better or one is a little bit worse Bernhardian colleagues in 2022 showed that the CEM size measurements correlate highly with the size measurements on MRI and studies show variable rates of over and under estimates for contrast may amount of MRI but always very similar so it's hard to say do they overestimate it by a few millimeters do they underestimate it by a few millimeters I don't know what the exact answer for this is because the data is kind of like I said very variable but the take on point is that these two imaging exams are very similar and that we can use contrast enhancement therapy as an alternative to MRI for any chemotherapy treatment or so especially for sure if you don't have MRI for sure for sure so now we're going to look at recalls which is an area that I really love using it for especially for architectural distortion so this was a really amazing case a colleague of mine recalled this patient for exceptionally subtle distortion that was marked here by the yellow arrows on Tomo really subtle we brought her back for contrast enhancement why do I like it well if it's subtle distortion right we know that distortion is subjective sometimes right so somebody can think that there's something there and I can look at it and say I don't see it at all and then there's another group which is very obvious distortion we all know that there's something going on so for those subtle distortions we always have this balance of well what do we do if our diagnostic imaging is negative then do we still go for a biopsy that initially identified you know there's there's so much question about what the next step should be so the contrast mammogram helps us decide it gives more information to help triage is this something to worry about or not and then on the flip side if it's one of those obvious areas of architectural distortion it really helps for staging so this is an example of subtle distortion is this real is it not real we bring her back and look at that these are the recombined images which show a large area of segmental enhancement and this was absolutely real there's no question about it this was an invasive lobular cancer and we could tell that there was something to worry about in seconds minutes I should say the advantage minutes so the next example is recall for calcifications and I already mentioned that you're going to act on calcifications that are suspicious regardless of whether they're enhanced there's enhancement or not so the presence or absence of enhancement is only helpful if it's larger than the area of calcifications and it would impact your management this patient had a very large area of calcifications throughout the central upper part of her left breast you can see these calcifications here they're pleomorphic right these are coming out they were biopsied they're malignant we do a recombine image we see that there's associated enhancement so like what's the point of this well it's helped us know that there's no enhancement in the lower part of the breast right we can see that the enhancement and at least the disease is isolated to this area of calcification and it's also given us information about the right breast so when you consider evaluating or using contrast mammoth for calcifications it's really to say what how is this going to help me I'm already worried about the calcifications I'm a look I have to look for something more and if that additional information will help me then it's worth doing this was DCIS this was a recall for a possible mass so there was the possible mass you can see it better in the upper outer left breast you can see it better on the MLO view when you do the recombine images you can see that there's this very discrete mass I mean look at that this is a woman who has dense breast tissue hard to differentiate anything right if there's a subtle mass located within the dense breast tissue and then we do the recombine images and all the normal breast tissue goes away and we see the mass we see the size of it we see the extent of it and we can look at the contralateral breast and say okay this is really what we're talking about this one small area so now let's look at the data for architectural distortion again this is an area that I really love the talent colleagues published the first study on this in 2017 and they said that enhancement was associated with 30 I'm sorry with 29 of the 30 cancers so there was one cancer in their study that was not clearly associated with enhancement but that person had marked background paranormal enhancement so it's difficult to know if it really wasn't associated with enhancement or it just wasn't perceived to be associated with enhancement in 2021 there was another study done on architectural distortion and said that if there was no enhancement you do not have to worry about this thing so between these two the real take home is if there is no enhancement in a patient who has no background paranormal enhancement or very little background paranormal enhancement the likelihood that that is cancer is very very low once somebody has a lot of background paranormal enhancement where it can impact your perception your identification of abnormal enhancement you want to be a little bit more cautious we're looking at calcifications most invasive breast cancers enhance but there are some invasive or DCIS invasive cancers or DCS that may not enhance this is similar to MRI and so we want to evaluate calcifications with suspicious suspicious morphology regardless of enhancement and I talked already a little bit about when to use contrast enhancement for these cases next we'll talk about masses masses that are associated with enhancement are more likely to be moignant if a mass has no if you have a mass on a low energy exam and there's no associated enhancement the negative predictive value is very high and that's no different than if you see a mass on a 2D mammogram and you do an MRI and you see no enhancement that's the likelihood that that is a cancer is essentially zero I mean there is no the negative predictive value of an absence of enhancement for a mass is very very very high so we talked about some of the clinical indications how people are using it some of the data now we're going to talk about where things are headed in the future there are three main areas that we're talking about which is breast cancer screening using contrast memo in the diagnostic setting just to formalize those indications a little bit and then radio mix which is AI and machine learning and really really neat stuff is happening so we'll talk about breast cancer screening this is a topic that I think most of us who use contrast memo most of us most people who who see talks on contrast memo this is the area that we're most excited about especially for women who have dense breast tissue who are at high risk maybe they don't qualify for an MRI can we do a better job at finding breast cancers for these women above what we're already able to do for tomosynthesis with tomosynthesis and ultrasound so this is a patient who has it's high risk for breast cancer she had a contrast memo this is a screening exam you'll see the low energy images for negative and then we do the rate combined images and we can see a hormone receptor positive cancer in the right breast and so this is kind of what we're talking about we're talking about identifying cancers that we would otherwise miss on our conventional imaging I mean this is this is why we're excited about MRI so the problem is that the data is that is not yet there where we can do contrast memo for screening certainly it has not been FDA approved for this indication so let's talk about the data we have retrospective studies reader studies and then there's CMIS CMIS which is really really excellent that have already been CMIS is happening now but there are some retrospective and reader studies that are out so Soran and colleagues in 2018 compared contrast enhanced mammography the full exam low energy and rate combined images to the low energy alone which is kind of a surrogate from mammography and they found an additional 13 breast cancers per thousand women's brain 2019 the MSK group looked at their data for contrast memo and they found a cancer detection rate of 15 per thousand women's brain which is much higher than the standard cancer detection rate rates we typically talk about with memo or with Thomas synthesis which is about you know three to five three to six breast cancers per thousand there's also retrospective studies on women who have had a history of breast cancer those that are above average risk women who have dense breast history of lobular neuroplasia and they all say the same thing which is that contrast memo does a better job than conventional memo CMIS though is really going to be the test the trial that helps differentiate should we be doing this it's a prospective trial for multi-center trial what CMIS is doing it's recruiting about 2000 women these women are getting both tumble synthesis and contrast memo and it's going to be able to see what the difference is in cancer detection and also what the difference is in false positives because that impacts our view of whether this is a good screening test and they'll track you know contrast reactions and what so that we can really get an overall look at how this modality plays for women who have dense breast tissue the good and the bad and compare it and see if this is something we want to do the results of that should be out in a few years it's very exciting stay tuned my group published a trial more recently that compared contrast enhanced memo to MRI for breast cancer screening we had 132 CEM and MRI exams in an asymptomatic population of women 132 that's a huge number and we had 12 people 12 radiologists look at all of these exams and we compare the performance metrics and what we found as expected is that CEM performed a little bit worse than the full MRI protocol you can see CEM sensitivity was 89 percent whereas the full MRI was at 94 percent but look at the sensitivity of 2D mammography which was 75 percent much lower we found that the specificity of contrast mammary was higher than the full MRI protocol which again is what we'd expect fewer false positives when we see something on an MRI on a contrast mammary it's more likely to be breast cancer and when we look at that metric of accuracy which is egg UC to see how what the balance is between cancer detection and not finding benign things we see that actually that the accuracy is very similar between both of these exams and we confirmed that contrast enhanced mammography is non-inferior to breast MRI and this was great I mean we looked at a lot of cases and we had a lot of people look at it and so this helps perpetuate the idea move forward the idea that these two exams are very very similar overall unfortunately again as I mentioned before we don't have enough data yet to really embrace this fully for breast cancer screening certainly the organizations that guide us have not done so and so really where we're at for screening is the ACR has acknowledged that CM has value but that there's limited data and so it's really only recommending it when MRI cannot be performed I imagine this will change over time but this is where we stand today the NCCN which is the National Comprehensive Cancer Network has a similar approach really use contrast mammoth for breast cancer screening when you can't perform an MRI same thing with USOBI which is the European Society of Breast Imaging so that's kind of where we're at I imagine that will things will change over time as I mentioned another area to for the future if there's a we're going to look at how contrast mammoth specifically applies to palpable lumps pathologic nipple discharge high risk screening evaluation and screening recalls more studies to see to see how it compares to our standard of care there's a great trial called it's called the RACER trial rapid access to contrasting hand spectral mammography and women recalled from breast cancer screening this trial is doing is randomizing patients to standard of care which is mammography ultrasound versus CEM and they're going to look at what the different performance is in terms of cancer detection follow-ups, biases, etc. missed cancers so that is going to be really one of this is going to the results of this trial are going to be really great to help us figure out is contrast mammoth better maybe it has a slightly better or better cancer detection rate but maybe there are other challenges that we need to be mindful of lastly for future directions we're going to talk about radiomics radiomics are really looking at differentiating cancer subtypes trying to figure out can we use contrast mammoth and the contrast that we see on these images to differentiate the nine from malignant disease and lastly to evaluate x-ray metastasies overall the wonderful thing is that CEM guided corbiopsy is now available you can get it it's amazing I'll show you an example of how that's used I know we're running out of time so this was a patient who had a recombined only finding let me show you so this was a patient who had architectural distortion in the left breast marked by that yellow arrow and we did a biopsy a tomosynthesis guided biopsy and you'll see that our clip is actually not where the tomosynthesis where the architectural distortion was so we weren't sure what to do about this did we sample appropriately the distortion and the clip moved or were we just off and this can happen with tomosynthesis guided biopsy I imagine everybody on the call or at least many people on the call have had this issue so we did a contrast mammoth to get more information and we found that there was no enhancement in the area of distortion which is great but there was enhancement in the right breast the enhancement here marked by the pink color was a fibridinoma a known fibridinoma but you'll see that there was actually an incidental enhancement in the outer central right breast and this was this was a malignancy so but what were you know what are we going to do with this thing we sent her to ultrasound we couldn't find it there was no associate correlate on the low energy exam so we had to send this patient to MRI but now with contrast enhanced mammoth biopsy we'll be able to do that another notable change is that there's now a lexicon for how to interpret the imaging findings which obviously I've not gone into any information about how to interpret the images that we see mostly the lexicon is based on is built around the low energy images being similar to mammography and the recombined images being similar to MRI so the lexicon is really geared towards mammography and MRI characteristics the main changes are that there's now no focus there's no that the term focus is not included in the CM lexicon we don't have the characteristics of dark internal cetaceans clustered ring and we've added a term called enhancing asymmetry which is the finding that you see an area of enhancement that you see only in one view and so with that this is the summary of the talk I'm actually not going to stay on this slide too long because I know we're running out of time and I want to give people a chance to ask some questions so you can always learn more these are some there are some books available websites journal articles and feel free to reach out with questions anytime thanks so much for your lecture Dr. Phillips at this time we will open the floor for some questions you can submit those through the Q&A feature and we will try to get through as many as we can we have a few coming in and I will go ahead and open this up how much iodinated contrast do we administer for CEM? so the dose of contrast is largely so it's weight-based and so the actual dose is built around the patient who walks in the door so we weigh the patients and the imaging units you plug in the weight and it tells you what the dose should be often enough institutions have a maximum dose that they administer so our maximum dose is 150 ccs ml I should say the weight-based I'm sorry the weight-based calculation is 1.5 ccs per kilogram thank you if you work up in the asymmetry with CEM and see no enhancement how confident can you be that the asymmetry is benign? does it become by RADS 3 or by RADS 2? so that this is a really great question and it's one of the challenges of contrast mammos what do you do with these enhance what we call now enhancing asymmetries which are areas of enhancement on one view only and the answer is is really you need to be concerned about it I would not blow these off so typically what we do now is you look at your low energy images and you see if there's a mammocorrelant to help you figure out is this enhancement perhaps it's associated with an area on the 2D mammogram that's been there for 10 years in which case yes it's enhancing but you're using the other features to tell you no no it's enhancing associated with a benign binding but if you are not able to get a low energy correlate then you would do a targeted ultrasound but I would say you do not necessarily call it a by RADS 3 or by RADS 2 you would want to work it out and then if you absolutely have no correlate on your mammore or ultrasound then what we had been doing before CEM 5 C was actually sending the patient to MR to further evaluate it and now that CEM 5C is around you can do a CEM 5C very rarely do I follow it thank you does CEM have the same sensitivity for non-mass enhancement comparable to MRI this is in regard to high grade DCIS I don't have the answer for that question specifically to non-mass enhancement okay can you clarify does CEM only use 2D and not TOMO images yeah that's a great question so CEM is a planar exam it's just 2D so when the exam is applied think about your 2D mammos and that's exactly how it's done there's no TOMO suite there are people that are talking about contrast enhanced TOMO synthesis where during the TOMO suite you're performing your dual energy images there are people that have studied that but that's not available now got it we've got two questions in the insurance reimbursement billing area can you speak to your experience on this do you have to get pre-authorization prior to performing no okay no it's billed as a diagnostic mammogram plus the administration of contrast so it's just a dive MMO and then the contrast often enough depending on where you work hospital or non-hospital related you may or may not get reimbursed for the contrast the contrast is roughly like $12 so at the moment that is how it's billed and there's not typically an insurance coverage issue I hope that I've answered you know the people that have questions about reimbursement I hope I've answered them we all would like to get reimbursed more and have a dedicated CTT code for it but that's not that's not happening that's not the thing yet all right does the compression affect the enhancement I think whoever asked that question I'm interested to know to know what you're specifically asking about so the degree of compression I can't answer I can only say that a contrast mammogram is done where you administer the contrast of the patient sitting and then you do the mammogram so the patient gets put in compression after the contrast is administered that is how these exams are done and so at the moment it does not seem to impact our the ability of seeing the enhancement now I cannot answer the question about like the degree of compression and how it entails me in your experience with any surgeons have they liked CEM versus pre-op MRI oh my god our surgeons love it every surgeon that I spoke into has loved it and I think that the challenge the the reason why the surgeons love it is because one of the challenges of MRI yes MRI is an amazing tool and I really don't want to diminish it because it's been you know an amazing boon for our for our field it finds many cancers but it also finds a lot a lot of non-cancers and these women are going for more biases more stress which is associated with more stress and so our surgeons are really liking it because if we see an abnormality we can do something about it there are fewer false positives fewer extra visits and so they appreciate the ability to identify just what we need to know and not anything more surgeons love it and it doesn't delay care you know you can do it right in the mammoth suite but they're talking about it at their conferences too contrast mammoth can we do dynamic contrast enhanced study enhancement curve with CEM so um that is not a part of the exam currently we do not do that currently there are a number of studies that have looked at looking at how the breast takes up contrast or how a lesion takes up contrast over time to help us differentiate cancer from non-cancer that has not been included in our current interpretation of the exam it's not as consistent as it is with MRI where you're looking at the breast you know you're looking at every portion of the breast at a same time you know at the same time over multiple time periods what do you do with multiple small foci of less than five millimeters of enhancement on MRI or on contrast mammoth I think it's about contrast mammoth so so this isn't also an interesting question because with MRI when MRI was started there were a lot more follow-ups and the reason why there were more follow-ups for this specific indication is because we didn't have the data to say oh this is just VPE versus not and I would say at the moment the the standard practice for this is variable among practices and how comfortable you are if you were to see multiple scattered enhancing foci none of which stood out as being definitively different than everything else I would just call it a virus too in background if there was one that really looked a little bit different or if I couldn't tell is there something here that I'm missing and I'm questioning certain areas then I would do a follow-up and comfortable doing a follow-up because I don't have the same amount of data long-term data to say oh this is really just all background being able to differentiate background from that from an abnormal enhancement so I would say the short answer is I am comfortable if I see multiple scattered areas of enhancement which we call foci less than five millimeters all throughout the breast calling it mark VPE and not doing more for it if there's one specific area I'm questioning something I would also feel comfortable doing a follow-up thank you all right I'll ask two more questions and we'll let you go you've got tons of questions here do you always repeat CEM after biopsy to confirm clip placement is that after a CEM biopsy if it's after a CEM biopsy I'm not able to answer that question we don't routinely in general I do not perform CEM after biopsy to confirm clip placement and for CEM biopsy I can't answer that because I don't do those so I cannot tell you what I would normally do is there a recommended timeframe for image acquisition in CEM after contrast administration so the standard thought is that two minutes from the start of the injection is when you start acquiring the pictures and you want an image within 10 minutes to make sure that the contrast material that's in the breast is still there hasn't washed out yet okay one more question in young patients with breast cancer do you prefer MR over CEM so for newly diagnosed breast cancer I would say that currently my answer largely has to do with logistics and it has to do with when the patient's going to be able to come in for the MR when the patient's going to be able to come in for contrast often enough if I see a young woman who's coming in we will do the contrast mammal right at the time of the diagnostic exam and so I don't actually have to bring the patient back for a contrast mammal or an MRI if I've already done a workup and then I've diagnosed the cancer and I'm now doing a contrast study for extent of disease it really would be a logistical choice and the location of the cancer so if the cancer is located deep within the breast or medial then I would choose MRI thank you Dr. Phillips for answering all those questions and thank you for your lecture today that was wonderful appreciate you being here absolutely I'm happy to if anybody has any other questions I don't know I really have not been following to see what other questions there are but anybody should feel free to reach out awesome thanks to everyone else for participating in our new conference today and all the amazing questions you can 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