Ultrasound Elasticity - SD

Introduction and Disclosures

I am Richard Barr, professor of radiology at Northeast Ohio University Colleges of Medicine and radiologists for radiology consultants in Youngstown, Ohio.

Today I'll be giving you a lecture on how we do elastography.

Hello, I'm Richard Barr, from Youngstown, Ohio. I'm gonna give you a lecture on ultrasound elasticity, in the breast, reviewing our work that we've done in with this technique.

Before we start, I would like to disclose that I am on the advisory boards and have received equipment grams from both Siemens ultrasound and Phillips ultrasound.

You should also recognize that Elastography is a new and rapidly evolving technology, and some of the technology discussed in this talk may not be approved for clinical use in some countries. I advise you to check with your clinical applications person for your manufacturer, to determine if the techniques that we're talking about today, are available or approved in your country.

Objectives

The objectives, for this talk is one, to provide the historical background of elasticity imaging. Discuss the principles of elasticity imaging without using any equations. Explain differences between compression elastography and ShearWave elastography. Review initial results of elasticity imaging of the breast and discuss limitations of the technique.

What is Elasticity Imaging?

What is elasticity imaging? It is an ultrasound image that is based not on the anatomy, like B mode imaging, but actually on the stiffness of tissues. You can consider it as the imaging equivalent of a physical exam. So what we feel with a finger when we do a clinical exam, we're using the ultrasound waves to do, with ultrasound and generate a, picture of that physical exam.

There are two types of elastography that we're gonna talk about today.

Compression Elastography

One is compression elastography With this technique, the stiffness of, tissue is calculated based on the displacement of the tissue with a compressive force. In other words, we're going to apply some pressure, on the tissues and we're gonna see how they move and use ultrasound to determine how they move, to decide if they're hard or soft. This technique is qualitative. It provides us how stiff or hard something is to the other objects that are in the field of view.

ShearWave Elastography

Another technique is called ShearWave elastography. In this technique, an ultrasound push pulse is applied to tissue and conventional ultrasound is used to measure the speed of the shear wave that propagates through the tissue From this speed of sound through the tissue, the strain modulus can be calculated in this technique. Since we know the amount of force that was applied, we can come up with a quantitative measurement of how hard or soft a tissue is.

Imaging Setup for Displacement Elastography

A imaging of the brass is performed with a conventional ultrasound unit and standard ultrasound breast probes, for the displacement, elastography. The software analysis of frame to frame differences and deformation of the tissue with mild compression allows for the display of stiffness or hardness of a lesion.

The strain image In this slide, you can see the image on the left shows the B mode image. And here we have a lesion that is iso coic to the surrounding background. So the lesion is not very conspicuous on B mode imaging. However, the lesion is very hard compared to the background tissue. And we do displacement elastography. You can see that we can see the lesion much better because it shows up as being hard compared to a soft background.

Analogy for Displacement Elastography

An easy way of explaining what we're doing or what the algorithm is doing in determining the displacement elastography is to consider an almond in a, bowl of jelly, or jello, excuse me. If we deformed the jello with, in this case a spoon, we change the shape of the jello 'cause it's soft, it moves. However, the almond is hard, and no matter how hard we push, we don't change the shape of the almond. So what the ultrasound system does is looks at the frame to frame differences when we're applying the pressure. And if the tissues change shape, like the jello in this case, it codes it as being soft. If it's hard like the almond and does not change shape, the algorithm considers it to be hard and therefore codes it as being hard.

Historical Background and Early Work

Crops did, some work with, tissues, for, many, many tissue types. And one of the things that he found was for breast lesions and looking at the elasticity properties, the cancerous and non-cancerous lesions had a large difference between them with very little overlap. And the difference, was on the factor of 1000 to 5,000. Based on this, basic physics information, we should be able to do very well in distinguishing benign mal lesions from malignant lesions on, elastography of the breast. Unfortunately, this wide difference with very little overlap, does not occur, as well in other tissues. So although this technique can be applied to many tissues, it will probably be best utilized in the breast.

Early work. In evaluating elasticity imaging, the breast was found to have limited use in a clinical setting. However these techniques used in these studies suffered in that the technique was not realtime and there was suboptimal resolution based on the equipment. With the recent development of realtime elasticity systems, which have a realtime dual display of both the B mode image and the elasticity imaging, and significant improved spatial resolution, the technique is now ready for clinical use.

Limitations of Compression Elastography

The compression elastic graham generated displays the relative stiffness to the rest of the image. Therefore, a given tissue will have a different shade of gray in each ela. Depending on what other tissues are in the field of view, fat in an entirely fatty breast will appear darker than in a very dense breast. Because of this, limitation of the technique and because of this limitation, it's gonna be very difficult to use compression elastography, at is as it is presently performed as a screening examination.

This is an example, to show you how tissues can appear in different shades of gray or colors if you're using them. Based on what's in the field of view. In this first image, we have a fat lole that's surrounded by dense breast tissue, a little bit of fatty tissue anteriorly and muscle posteriorly. And as you would predict on the ELAs agram, which is shown on the image on the right, you can see that the fat shows up as being white, meaning it's much softer than the surrounding tissues. However, in the second case in the bottom where almost the entire image is fat, this area fat that I've circled in red shows up as being black because it is the stiffest fat within the image

Technique Importance

Technique is, very important in getting optimal images. And this technique actually changed based on manufacturers. Some manufacturers equipment requires very little or no compression, while others require some manual compression and release to generate an appropriate ELAs gram. So one manufactures, equipment, to may get an optimal image where on another manufacturer is using the same technique, you may not even generate an ELAs gram.

For our system, we select to display hard lesions or less strain is black and soft lesions, or more strain is white. Thus in general, fat is going to be depicted as a white lesion, and cancers are going to be depicted as black lesions.

We can use color maps. They are available and there are several maps available. My personal preference is to use black and white for compression elastography because it's a relative technique, and I feel that I can interpret the images better using black and white. When we talk about ShearWave imaging, where we get an absolute, number, which color codes the pixels, in that case color can be very useful, in providing a very, easy way to interpret the images.

Case Example: Invasive Ductal Carcinoma

This is a case of an invasive ductal carcinoma. I just wanna review how the images are displayed, for your, interpretation. On the left side of the image are standard B mode image. There is a field of view box, which is the field of view that we're gonna be used to generate the ELAs on. The image on the right is the ela, and again, we're using hard, as black and soft as white.

In this system, there's also a quality factor, that gives us a number that corresponds to, how well we're in the range of appropriate displacement to generate a adequate image. I will say that there are other factors other than this quality factor to generate a good image, which we'll be talking about. So having a high quality factor does not necessarily mean that you're going to have, the optimal image.

You can see in this, case on the BMO image, this is, clearly a birads five, lesion. And you can see on the ELAs, we can, see the lesion quite well. We can see, good distinct borders, and we can see that the lesion appears slightly larger on the ELAs agram than it does on the B mode image. And we'll discuss, that, finding, shortly.

Also want you to note that when we have shadowing from this tumor, we don't see that in the ELAs Graham, that artifact does not transpose over, into the ELAs Graham.

Importance of Maintaining Lesion in Plane

So, the technique, that we use, the algorithm within the system requires that the strain changes to remain in plain. In other words, because we're comparing how the lesion changes with, displacement, if the lesion moves out of the plane, the image, that we, use to interpret will therefore see a change that actually didn't occur. It was because the lesion moved in and out of the plane, and therefore give us inaccurate, ELAs gram.

So, it's very important that you monitor the beam mode images. You're doing the ELAs to make sure that the lesion remains in the imaging plane and does not change during the time you're collecting the, ELAs.

In general, we like to obtain a short clip of the ELAs and then go back and do our appropriate measurements. We do this, routinely in all our clinical cases, and I do not like to have the patient wait while we do a lot of measurements. So we tend to do the least amount of measurements while the patient is there to, determine what we're gonna do with the patient, and, move on with that.

And then we can come back with the stored image clip and, do further measurements if we're going to do, research and want to get some additional information.

In general, what we found is the longer you take, doing measurements and looking at the screen, the more anxious the patient gets because they think you see something, that is concerning. And it really raises their anxiety. So, we really try to do, the most, efficient, imaging and measurements we can, while the patient is there to do the appropriate, management.

And like I said, save clips, and for research measurements, we do those, after the patient has left the technique we use, we try to, limit the patient, motion and the keeping the lesion in the plane by having the, probe and the lesion perpendicular to gravity. So we tend to roll the patient so we have the, probe, the lesion and the table all in one straight line.

This also helps because for the systems we use, we need very, very little motion and we try to set this up so it's the patient's breathing and heartbeat that causes the displacement. And again, we want that to be in line with the lesion and the probe so that the lesion is moving, up and down in the field of view and not right to left. And, with some practice, you can acquire this technique, very easily.

For most patients, what we found is to get adequate images, we just need to have the patient do normal breathing, and between the heartbeat and the breathing, that is, all the amount of displacement we need to generate a good ELAs gram.

As we said in the beginning of the talk, different manufacturers require different amounts of compression. I will say with the systems that we have, have, the two extremes are patients that have very small breaths. The breathing may actually cause too much displacement, and we do not, get a good ELAs agram. In that case, I actually have the patient, hold their breath and try to hold the probes still as possible to get a good ELAs agram.

The other extreme is patients with very large breasts, where it's very difficult to have the, lesion and the probe aligned and the breast may be hanging off to the side of the patient. And in that case, we do have to apply a, small amount of, rhythmic, compression and decompression to generate the ELAs.

And it's a technique can be that can be easily learned, but does require, some practice.

Tips for Optimal Images

Some tips to help you generate. The most optimal images are to keep the field of view as large as you can, and try to include fat normal breast tissue in the lesion because we're doing a comparison of different tissues. This allows you to compare the elasticity properties of the lesion to both fat and normal tissue. If the lesion is a cancer, it will be much harder than both fat and normal tissue and show up black with fat and normal tissue showing up as white or light gray.

If the lesion is benign, it will have similar elasticity characteristics to the normal breast tissue and will be slightly, darker than the fat, but will be approximately the same, shade of gray as the normal breast tissue.

We really like to look at the B mode image when we're doing these. And again, it's to help you get an idea of the amount of displacement of tissues that you're getting. And with practice, you'll learn what the appropriate amount of displacement is. And also looking at the B mode image just helps you stay, so that the lesion remains in the same plane.

One of the things when we started elastin imaging, we were concerned, does it matter where on the lesion you do this examination? And this is a case of a invasive ductal cancer. And what we did is scan the lesion in multiple different, planes and in multiple directions, and we get the same results no matter where we are scanning.

Lesion Size Changes

I mentioned earlier that, in the cancer we showed before that the cancers tend to show up larger on the ELAs agram than they do on the B mode image. And we have seen cancers that have been three, almost four times as large on the ELAs as they have been on the B mode image. And it's important that you recognize this because if you have a lesion that is two centimeters and it gets, three times larger, it's now six centimeters in size and completely envelops the field of view of the ELAs agram, and you will not be able to see the borders of the lesion, and therefore not be able to get accurate measurements, and maybe confused as to know, even know where the lesion is.

So what we try to do is pick a position in the larger lesions so that the lesion that we're doing the ELAs agram on is about one to one and a half centimeters in size. And this allows us to make sure that on the ELAs agram we can see the borders of the lesion.

There are several different measurements you can use to determine, the size changes in lesions. And again, we've talked about that. Breast cancers appear larger, on the, ELAs agram and actually benign lesions appear smaller, and each manufacturer has, their own way of you getting measurements.

What you can do is, we usually measure the lesion on the B mode image, and then we use what's called the shadow function, which draws the same line in the same position on the ELAs agram. You can then change the measurement size, in that position to match the ELAs Graham, and the system will provide you with a ratio of the, ELAs agram to the B mode image.

You can use area measurements, or, volume measurements, they'll all work. We tend to use the length measurement, because it is the easiest for us to do, when the patient is there. And again, we use this clinically. So we really would like to, determine what the, treatment we're going to offer the patient is, so we can tell them that while they're on the table.

Case Example: Mucinous Cancer

This is a video clip of a mucinous cancer, on the B mode image. You can see the lesion is somewhat iso dense to the surrounding tissue, with some hypoechoic areas within it. But on the ELAs agram, you can see the borders of the lesion quite well.

You can also see that during this video clip that we can see the margins of the lesion on the ELAs agram throughout the cycle. And this is important because if you are not getting this quality of images, you're having some problems with your technique and you need to, talk to your applications person to, make sure you're getting adequate technique.

What we found in, mucinous cancers is that the ratio is, one or slightly larger in these lesions. So it, we don't see the changes that we see. With invasive ductal cancers.

Pre-Compression Importance

One thing that we found is probably the most important factor in acquiring optimal ELAs is something called pre compression. The ELAs image that you generate is significantly affected by the amount of pre compression or how much pressure you you use when you're obtaining the image. As you apply additional pressure pushing the probe onto the breast, the tissues beneath the probe becomes stiffer and therefore give you different results.

And this video clip, I'm was gonna try to explain this, technique to you. I'll start the clip again shortly, but here we have on the left our beam mode image. And what I want you to notice is, this rib, as well as a lesion that's sitting right here, which is a epidermoid cyst.

For the first time I start this clip, I want you to just look at the B mode image. What I'm going to do is I'm gonna start the clip with a lot of compression, probably more than anyone uses, in, generating their B mode images. And as we go through that clip, I'm gonna be releasing pressure, and I want you to just to look at this rib. So we started here, and you can see as I'm pulling back on the probe and lifting up, we're getting less and less pre compression.

Now I'm gonna start the clip again, and this time let's look at the ELAs gram. You can see when we start, and I have a lot of recompression, we don't see the lesion at all as we get to the middle, we can see the lesion occasionally, but not throughout the whole clip. And at the end, we can see the lesion quite well.

And I just pulled out, three areas from those clips so we can, discuss them a little bit better, and look at them. So again, we have significant pre compression, mild pre compression, which is actually where I consider I do my standard B mode imaging, because I think we need a little bit of pre compression to actually get optimal B mode images and very minimal pre compression where I do my imaging for the ELAs gram.

And again, you can see with compression, you can see this, epidermoid cyst better with, compression, because it lays out the tissues better. It also, changes the Cooper's ligaments, so we have less artifacts. So again, when we're doing B mode imaging, we actually like to use this pre compression.

But you can see here I have the rib at approximately 1.2 centimeters, and our ELAs agram is basically all noise. As we move to mild compression, you can see the rib is now dropped to about 1.7 centimeters. We can still see the, lesion fairly well. And you can see on the ELAs that we don't see, a really good gram as we go through a clip. It'll appear well on some frames and poorly on others as we go to very minimal compression.

You can see that the rib has dropped almost two centimeters in depth. The lesion doesn't show up quite as well on the B mode image because we're using less compression, but we get a really excellent ELAs gram.

So my recommendation is, initially when you're doing your work, you'll do your standard B mode imaging using your amount of pre compression, which, you feel you generate the optimal images. And after you've done your standard exam with B mode imaging and color, then you can move on to the ELAs.

You should also realize that when you're doing, color imaging, you will get much better color doppler imaging if you use, this minimal amount of pre compression. Also, because as you apply compression, you occlude vessels, and you, also then for, decrease the amount of color flow doppler you're going to see.

And just to show you, that I didn't make this up, this is the same patient, and I'm doing this clip again and I'm just applying here. We again, we got this rib at two centimeters. So you can see I'm doing the same lesion with very minimal pre compression. And you can see throughout the whole clip, we can see the, lesion on the ELAs very well.

So my recommendation is when you do your B mode image, when you're done and you wanna do your ELAs agram, choose something in the image and just slowly lift up on your probe. And as you do that, you'll see what you're looking at, drop deeper and deeper into the field of view. And what you wanna do is make that fall as far down in the field of view as you can and still get a, image, that will allow you to apply the appropriate amount of pre compression and get reproducible. Excellent. Elast grams.

Size Measurements and Literature Review

We talked about the size measurements, and I just want to go over, the literature regarding that. Tim Hall in 2001, was the first to recognize that there was a size change with cancers. And he used a EI or ELA measurement to the B mode image. He used area and he came up with a ratio of 1.2, so if the ELA image, was 1.2 or larger than the B mode area, that they had a hundred percent sensitivity of this predicting a malignancy and had a specificity of 75%.

Pilot Study Results

We did a, a initial pilot study, with the system, where, we used the technique that I've described, and we chose to use a ratio, a length ratio of 1.0. So if a lesion on the ELAs agram was, the same as or greater than on the B mode image, we called it a malignancy. If it was less than one, we called it benign.

And in that study that, we presented at the RSNA in 2006 and has, recently been published in ultrasound quarterly, we looked at 123 patients who were coming to us, for an ultrasound guided biopsy. All the patients had core biopsies and pathology. Of the 123 patients, that we biopsied, 106 of those were benign and 17 were malignant.

When we looked at the ELAs Graham of the 106 pathologically benign lesions, 105 of them had a ELAs to B mode ratio, of less than one, giving us a specificity of 99%. All 17 malignancies, had a ELAs to B mode ratio of greater than one giving us a sensitivity of 100%.

So these were, very, excellent, results, and we wanted to see if these were reproducible in other labs.

Multicenter Trial Results

We therefore did a, a multicenter, multinational trial, where we enrolled 635 patients, all of which were female with an average age of 56. And again, it was the same, study. All these patients were being referred for an ultrasound guided biopsy. They had their standard ultrasound examination, they had an ELAs gram performed. The site investigator, determined the EI to BI ratio. And then we got the pathology, from, core biopsies or, FNA.

Of the 635 patients, 65% or 413 were benign lesions. 35% or 222 were malignant lesions. And as these were basically all comers to all the labs in the study, we had a, really good distribution of pathology and a standard distribution of pathology, that one would see in a, standard breast care clinic.

The results are for each of the six sites, the number of lesions that were biopsied, how many of those lesions were benign of the benign lesions, how many had a EI to B mode length ratio of less than one, how many, pathology were malignant? And of those malignant lesions, how many had a, a EI to B mode ratio of equal to or greater than one?

And you can see if we look at the specificity, that is, how many of the benign lesions on pathology had a ratio of less than one? The, ranges, were varied between 67% and 97%, with an average, specificity of 87%, which is, actually, very excellent.

If we look at the malignant lesions, all centers except one had a hundred percent, sensitivity. The one center that actually, did not have a hundred percent, had 97% of their 90 malignancies. Three of those, had a ratio of less than one. So that gives us an overall sensitivity of 98.6%.

After the study was done, and the cases were reviewed, the three lesions that, appeared smaller on the ELAs agram, was a case of invasive ductal cancer, a lobular cancer, and a mucinous cancer. And in retrospect, it is probably that the measurements on the B mode image were probably inaccurate. And again, I think one of the key points you need to, use is you cannot use this length change measurement if you do not see the lesion very well on both the B mode image as well as the ELAs agram.

And we presented these results at the RSNA, in 2007. And from that study, these were our results. For the benign lesions, the EI to B mode ratio went from 0.2 to 1.5 and average 0.76, the malignant lesions went from 0.9 to 3.1. And again, if we remove those three cases that were probably measured incorrectly, that ratio would've gone from 1.0 to 3.1.

These results were extremely significant. And, you can see from the scatter plot that we, with the ratio of one actually do get a very good separation of the benign and malignant lesions.

Bullseye Artifact for Cysts

Another interesting observation that, r Lab made, during our initial studies, with this, was that both simple cysts and complicated cysts had a very characteristic ELAs gram. They both had what I call a bullseye appearance, which is a white spot in a, black lesion and the posterior white spot.

We also noted that four lesions that on BMO we thought were solid and referred for, biopsy also had this bullseye appearance and on biopsy, all of these supposedly solid lesions turned out to be complicated cysts.

Here's an example of this, which we know is now a, artifact, a simple cyst on the B mode image. And again, you can see the lesion shows up as a black ring with a white central area and a white area posterior to the lesion.

We wanted to determine, if this lesion, could be used clinically, and it had a high sensitivity and specificity, for evaluation of cystic lesions. So we looked at 127, consecutive patients who appeared in our lab that had this, bullseye artifact. And the sizes range from two millimeters to 40 millimeters with a mean of nine millimeters.

Of these 127 lesions, 62 or approximately half were biopsied and pathologically confirmed as simple or benign complicated cysts. The other half or 65 of the lesions were simple cysts based on B mode criteria, and therefore were not biopsied.

If we look at the, 62 lesions that, were biopsied that did not meet the criteria for being a simple cyst on B mode image, 56 or 90% of them, we knew on the B mode image, were most likely complicated cysts. And actually six or 10% of those had an appearance, which we thought, the lesion was solid on B mode imaging.

I just wanted to show you, another set of slides. If you're using different systems, you need to check with your manufacturer, to make sure that this artifact does occur on their systems. And I'm showing you here images from a Phillips system, which has multiple, settings for elasticity imaging if you use their setting. Number two, you get the bullseye appearance as we've talked about the white central dot, the black lesion, and the white peripheral zone.

If you use their elasticity setting, number one, you see the lesion as black. You do not see the central white spot, but you do see the peripheral white zone. They also have, another setting called AI or anti coic imaging, in which the, cystic contents would show up as, yellow on a black background.

Hitachi Score System

I do wanna mention that there were other skills, used to grade images, and I'd like to mention the Hitachi score. They use a, score system that is, more set to, kind of a BIRAD score, which goes from one to five.

And if you look, let's start at, five, their score five is a lesion that appears larger than the B mode image, and it's harder their image. Number four, the lesion is harder, but is the same size as the lesion. So again, their, score four and five corresponds to are saying that a lesion is equal to or greater than one, and therefore, is suspicious and needs further work.

Their, BIRAD scores one, two, and three. The lesion is, either soft, or modeled and, for their birad three, the lesion may be hard, but it actually gets smaller corresponding to are, less than, ratio of less than one, and therefore probably benign.

And they see an artifact in their cysts, which they have this, tricolored, blue green red on their, color coded, ELAs gram

Semi-Quantitative Methods

Because compression elastography is qualitative and not quantitative. Investigators have looked at, a way of trying to make this semi-quantitative. And one way you can do that is to compare the ratio of the, lesions, to fat. So, you can, on the system, depending on which country you're in, draw a region of interest in the lesion in a region of interest in fat, and you can compare the, stiffness of those two lesions, and therefore obtain a ratio of how hard the lesion is compared to fat.

There was a nice study presented at RSNA in 2008, that looked at this, and they found that a ratio of less than 4.8, corresponded to a benign lesion and a ratio of 4.8 or larger corresponded to a malignant lesion.

Pre compression is critical, in determining these measurements. And the amount of pre compression, needs to be minimal and needs to be the same when you do this measurement. Therefore, the, areas that you use for the field of view should be, at the same field of depth, I'm sorry, field of depth if possible. To give you the most accurate measurements,

Clinical Use of Elastography Imaging

Let me just review how I use EI imaging in our, breast care clinic. The most obvious is can we determine if a lesion is benign or malignant, which we've talked about before, and we can use, again, a length or area measurement. We can use this relative stiffness to fat, or you can use a color scale, like the Hitachi to determine if something is benign or malignant.

But in addition to that, we can look at the ELAs and, use information if the lesion is hard or soft to provide us some diagnostic information, such as, is the lesion really a fat lole? Is the lesion, iso an iso coic area on the B mode image? And there actually is a lesion present. Is the a lesion that's iso coic on the BE mode image, really a complicated cyst, can we use the ELAs agram to help us better define where to do a biopsy? And is there some characteristic information, within the ELAs, that may tell us, some histopathology, regarding the lesion?

Example: Fat Lobule

So this first example, I showed you before. This is a patient that was referred to us, because this hypoechoic, lobular mass in this dense breast tissue was referred to us for an ultrasound guided biopsy. When we did the ela, you could see that this is an extremely soft lesion and is, is, iso hard or the similar hardness to other fat in the lesion. And this is actually just a fat lo, and does not need to have a biopsy. This is a, a lipoma.

And again, this is an example that this is a qualitative technique, not a quantitative technique. Although the lesion is here and, is different than we see in the background fat, on the ELAs gram, it shows up as being the same intensity as the fat. But it does have this white ring around it. And this actually white ring is a artifact.

And I can say this 'cause I did the images. These, were not properly obtained images because this lesion was moving in and out of the field of view, when we were doing the examination. And this, ring artifact is because the lesion was moving in and out of plane. And therefore, this artifact actually can be used to help us determine benign lesions as malignant lesions are fixed to the adjacent structures, and do not move independently from the adjacent tissues.

In this case, this lipoma is encapsulated and is as we compress the, lipoma is moving in and out of the plane, differently than the adjacent tissues are. And that would pro what provides us this, ring guard effect.

Example: Palpable Mass - Complicated Cyst

This poor woman, had gone to two other centers before she came to us. She presented, she had a clearly palpable mass that everyone could feel her mammogram was negative. She had two other ultrasounds, they were negative. We did an ultrasound, this is the B mode image. And without the ELAs, I also would have been, call this a negative exam.

We knew where the lesion was because it was clearly palpable. When we do the ELAs, you can see that we clearly get the bullseye cyst artifact. We aspirated this, lesion. It completely disappeared. The palpable mass went away. There was no residual, tissue left on the B mode image and on pathology. This was just a complicated cyst.

Example: Shadowing in Cancers

I've mentioned this before, but I think it's, another interesting thing, that can help you, when you're trying to decide where to do a biopsy. In a lot of these, larger, harder cancers, we do get a lot of shadowing on the B mode image, and it's very difficult to determine exactly, where the posterior border of the malignancy is. The shadowing artifact does not occur on the ELAs agram, so you can clearly define the posterior margin of the, tumor.

We've talked about the cancers appearing larger than on the B mode image. It's unclear to me if the ELAs agram actually is a better predictor of the size of the lesion versus the B mode image. There is some work going on to determine, if that is the case. And again, this size change, may predict, some features of the cancer, in regards to its aggressiveness.

Example: Lesion with Benign and Malignant Components

This is an interesting case. This patient had a lesion on mammography that was clearly visible. If possible, we tried to do all our biopsies under ultrasound, so we brought the patient to ultrasound. This was the lesion. And again, without having the mammogram, knowing where the lesion was, it would be very difficult just based on the B mode image for us to be confident that this was the lesion.

But I do wanna show you a couple features of this lesion. One is in red eye circled what I'm gonna call a head to the lesion. And with the green arrow, I'm pointing to a little tail from the lesion. So when we do our ELAs agram, you can see the lesion now is much harder than the surrounding tissues. And, we can see the tail much better.

The problem is when we look at the head of the lesion, the head of the lesion is very soft and blends in with the surrounding tissues. So this was very puzzling to us. We did the biopsy of this lesion. It was an invasive ductal carcinoma. She had a, a lumpectomy. And after that lumpectomy, we went to the pathologist and said, could you review this with us? Because, we couldn't figure out what was going on.

And it turns out that this, head that we have circled in red was actually a benign fibroadenoma that was attached to, or adjacent to the invasive ductal cancer. So the ELAs Graham actually was correct. This head was actually benign fibroadenoma and just blended in with the normal background.

So again, you can use the ELA to help you to decide where to biopsy, because if we had just biopsied this area, then we would've come back that the lesion was a benign fibroadenoma and made an inaccurate diagnosis.

I will say that I did have another case, where we had a six millimeter, malignancy that was adjacent to a six millimeter fibroadenoma. And on the B mode image, the ultrasound acoustical properties of the two were very similar, and they appeared as one lesion. When we did the ELAs gram, we kept getting conflicting results. The lesion got larger or got smaller. And again, we were very confused. We, did a biopsy of the patient, it came back malignant, patient went to surgery.

We looked at the specimen and to find out that again, it was, basically two lesions, not one that were very similar in size. One, a benign fibroadenoma, the other in invasive ductal cancer. So, you need to keep this in mind. And when you are having problems at your ELAs gram, keep this in mind that on the B mode image, maybe there's not one lesion, but two lesions. And the BMO image is providing you some information, to determine that.

Example: Benign Fibroadenoma

I just wanted to show you a benign fibroadenoma. This is kind of a taller than wider, lobular mass on the B mode image. So a birads four lesion, you can see it clearly gets smaller on the ELAs gram. And, here again, we have some, these are, very old images. We do, again, get this artifact, a ring artifact around the lesion secondary to the lesion moving in and out a plane. When we acquire the images,

Example: Isoechoic Lesion - Complicated Cyst

This patient, had a mammogram screening mammogram. We noticed a, a lesion that was suspicious. We brought it ultrasound. This is the B mode ultrasound. And again, an iso coic lesion to the background, fat. But we knew where the lesion was on the mammogram, and it had, same size and configuration. So we were very confident that this was the lesion that we were seeing on the mammogram.

And again, very solid appearance looked speculated. We felt that this was, a birads four C or even a BIRADS five lesion. And you can see when we did the ELAs gram, we got the bullseye appearance. We did an FNA, we're able to aspirate the lesion. It disappeared on, the B mode image.

This was early in our experience, so we went ahead and actually did, core biopsy, to completely, remove that area, to make sure we were not missing anything. And on pathology, this came back to be a complicated cyst. And again, the core biopsy showed the, cyst wall, within it. So, there was no question that this was a benign, complicated cyst appearing as a suspicious, solid mass.

And I think this is important because our pathology department, if we, send this specimen to them and say that we are concerned about a, solid mass, and they do not see a reason on the pathology to explain a solid mass, they tend to put a statement in that further work is required. The lesion needs to be re-biopsied, or surgically excised.

And this puts us in a predicament. If we go back to look at the ultrasound, and this was a complicated cyst, it's now no longer present. And you have the dilemma of what do you do with this patient? Do you send them, for surgery to remove, a larger, specimen from that area? Do you follow them closely?

So again, knowing that this was not a solid mass, but a complicated cyst and passing that information to the pathologist, leads to, less confusion and, better, correlation between the radiology and pathology.

Example: Bloody Discharge - Invasive Papillary Malignancy

This was, an elderly lady that came in with a bloody discharge. She had a large mass on mammography. On ultrasound, we can see kind of a bi lobed lesion. It's very complex with some cystic areas and some solid areas. We did the gram, and you can see that the right side of the bi lobe lesion was very soft, but it did not have the cyst artifact.

The, left side of the lesion, got larger and was very hard. There was an air, excuse me, a fluid fluid level on this, right side on the B mode image. So we were, considering the sense the patient had a bloody discharge that maybe this was, blood components.

So what we did is we went in and aspirated this side, with a 20 gauge needle, and it was all, old thick blood. We then went in and cord, the solid portion of this lesion. And this was an invasive papillary, malignancy. And again, helpful information from the, ELAs agram showing you that this portion was probably benign, and very soft, and in this case blood. And this is the area that was hard and suspicious, to guide our biopsy.

Example: Solid Component in Cyst

We were very concerned because when we look at this bullseye artifact, although we did this study, we really did not have any, cystic carcinomas and we were concerned would this artifact, hide, a cystic neoplasm. And what we've seen this case is actually the smallest solid component within a cyst, that I've seen so far. And this is courtesy of Carmel Smith, from Australia.

You can see that there's a two millimeter inductal benign papillo in the cystic lesion, and you can see that the solid component, the papilloma appears smaller on the ELAs gram, and you can clearly see that solid component in the cyst artifact.

And we have seen many, many other lesions, since then, and we feel very confident that, if there is a solid component in the cyst, it will show up, as being a hard area within the bullseye artifact.

Another more recent example where we have a solid component, in the cystic lesion. And you can see we've got the bullseye artifact. And, here you can see that there's a solid component here, which, is harder but smaller. This was a benign, lesion, but again, we feel very confident.

Another thing I'll show you is there's a clearly another cyst artifact here corresponding to something in the B mode image here, which is isod dense. And what we have found is there are many isod dense cysts, within the breast that we really don't see very well on B mode imaging. So, if you see this artifact and there's no corresponding be mode image, we believe that there probably is a, cyst there, but it's probably benign and is a knot of clinical, significance.

Example: Lymph Node with Malignancy

An interesting case. We also decided to look at lymph nodes. We routinely look at lymph nodes in patients, that, we think have, cancers, to do, staging at our initial biopsy. This patient had a, somewhat normal appearing, lymph node other than being somewhat large, in her, level two area on ultrasound.

When we did the ELAs Graham, we saw this area in the upper pole, if you will, of the lymph node. That persistently was much harder, and, kind of deformed where the lymph node was. And again, I apologize, these were some of the furry first images we have, from probably about 10 years ago. So the image quality is not as good as now, but we were able to, you can keep elasticity imaging on, we used, a core needle and guided it with elasticity imaging to biopsy this area. And this was a foci of, malignancy, within the lymph node.

Example: Hypoechoic Mass - Complicated Cyst

Another interesting case, again, the patient, came in, had her screening mammogram. There was a lesion we, we were concerned about. She came for a diagnostic ultrasound, and we found this, hypoechoic mass that had irregular borders, what appear to be speculations as well as shadowing. When we do the gram, we got a bullseye artifact.

So, we stuck a, 20 gauge needle into this lesion, completely aspirated it. The lesion disappeared. And again, this was early in our experience. We were very concerned because this, was, very suspicious on the, B mode imaging. We went back and did core biopsies through this area, and again, obtained, pathology findings of a complicated cyst, with a cyst wall in the core specimen and no other pathology.

So, we think that this bullseye artifact is very, very helpful. And, when we see it, even if a lesion appears to be solid, we try to aspirate the lesion first, thinking that it's going to be a cyst.

Limitations and Pitfalls

When we went back through our multicenter trial and we tried to figure out why the specificity, varied, between sites, and also, why it was about 85%, and where were our mistakes, what we found was that when you have a hypo coic lesion, such as fibrocystic change or fibroadenoma, that's sitting in an area of dense breast tissue like we have here on the B mode image.

So in red eye focused in on the fibrocystic change, which is hypo coic. And in the green we've got an area of more dense breast tissue. The elasticity properties of the fibrocystic change or fibroadenoma are very similar to the normal dense breast tissue. So when we do the ELAs Graham, it's very difficult for us to distinguish the interfaces between the benign tissue and the fibrocystic change.

So this was actually one of my mistakes in the multicenter trial because I interpreted this, what was fibrocystic change to increase to the whole size of this green area. We biopsied it and again, it came back fibrocystic change. Now looking backwards, this area here, these borders here, you can see kind of correspond to the shape of the fibrocystic area. And actually that area got smaller, but it, it is very difficult to interpret because the surrounding, areas are also the same.

And just as I showed you in one of the first slides that on a b mode image, we may have iso dense, a lesion may be isod dense in the background, and we have a very hard time seeing it with, b mode imaging. And it can be really clearly seen on elasticity imaging. The reverse is also true.

So, in especially benign diseases of the breast where the lesion is in dense breast tissue, it is sometimes very hard to interpret these images.

Other areas that we found out, again, we've had, several lesions now where when we do the ELAs gram, which we didn't realize initially, here, we're seeing that this on the B mode image is one lesion, and you can clearly see that there is a cyst attached to the lesion on the ELAs gram. And again, here you have a, a similar case. So we've seen this not infrequently.

You end up with a conundrum of where do you take your measurements. So you just need to be aware of this. And if you're concerned, you should always err on the side, of doing a biopsy.

ShearWave Elastography

I do wanna mention ShearWave elasticity or a shearography. And again, this is a quantitative measurement. This is where we put a ultrasound push pulse, and we generate a sheer wave through the tissue. In the sense it's the same as when we throw a pebble into a pond and we generate the waves coming out from where the stone goes in, and we can measure those waves, and as they go through the tissue, we can determine how hard or soft something is.

This is less operator dependent because we do not have to worry about displacing the tissue by, using compression. But again, pre compression does play some role in, affecting this. So you also need to be aware of that. And if you're using this technique, we also advise that you do the same thing and, make sure that you're applying very little pre compression when you, acquire the image.

And again, here, we like to display these in color because we have an absolute measure and, the color, really does signify some information.

Examples of ShearWave Imaging

Lemme just show you some examples. Here you have a obvious malignancy, on the B mode image. And you can see on the ShearWave ELAs agram, and we're plotting here, blue is soft, red is hard, and we actually have numerical measurements. This manufacturer likes to use kilopascals as the measurement of how stiff things are. And here you can see that the maximum is, actually well above 200 hundred kilopascals. And that signifies that it's extremely hard in, in a cancer.

It has some characteristic changes with the center is a little bit softer, but still have a very high measurement of approximately 70 kilopascals. You can contrast that to this image where we have, an iso coic, lesion, which on the, shear wave ELAs gram is blue and has a mean value of 25 kilopascals, meaning it's very soft, and is benign in this case, was a fibroadenoma.

Applications in Other Tissues

Can this technique be used in other tissues? Yes. It can be used anywhere. There's nothing specific about this technique, but again, specifically in compression elastography, we need to have the appropriate amount of displacement. And in ShearWave technology, we have to be able to put, push the pulse, I'm sorry, put a push pulse at the appropriate level to generate a ShearWave.

And these vary between tissues and tissues. In our experience, breast is probably the easiest, to do this. But it can be used in other tissues. We get superb images in the thyroid exam. Unfortunately I have not, found it to be clinically useful in terms of, when or when not to do a biopsy at this point. Further work is going on. But there are some benign thyroid lesions, which are very hard. And again, we may have overlap of tissue, and although it does provide us some information, it will not be as sensitive or specific as we see in breast.

A lot of work is going on with prostate. Hopefully this technique, would allow us to do much better in, imaging prostate cancer than what we presently have. And again, it's, it's too early to speculate if, that is gonna be the case.

I showed you an example of lymph nodes. It does work in lymph nodes and it actually can help you find foci of abnormalities within the lymph nodes. So there, it, it is, I think very useful. And, again, we use this in all our breast cases where we are looking at lymph nodes to determine, if we can stage the pa patient, by doing a lymph node biopsy at the time of doing the, regular biopsy work is being done to see if we can determine, the, efficacy of a radio frequency ablation. 'cause as we ablate the tissues, we change their elasticity properties.

My own, feeling about this is that, we are looking at relatively, large areas of tissue with the elasticity. And I don't think that the technique is going to be sensitive enough, to completely exclude leaving a small amount of tissue, that is viable. We find that, ultrasound contrast, probably is, going to be the method of choice, in that, feel for some time.

Another very, very, useful application is in liver fibrosis. We can, using the quantitative measurements, of sheer wave, to actually determine a stiffness number for the liver. And work is being, presently going on that we can correlate that with pathology. So we can determine the liver stiffness to give us an idea of where on the scale, of cirrhosis, or fatty liver change.

We can have, and this is a non-invasive test, and we can follow these patients in the, in the same area, in the liver over time. I think this is gonna be an excellent application.

Our initial work with focal liver lesions, however, has not been as rewarding. And we've had some problems. And again, I think there is a large overlap between the properties, of benign and malignant lesions on, their, elasticity. So although that we get some information, it's not gonna be as useful as we find in breast.

Conclusion

So at this time, I would like to conclude, and I think key things to walk away from this is that each manufacturer has a different algorithm that they're using to generate their displacement elasticity images, and you need to really work with that manufacturer to get the optimal technique.

It's important that when you're doing the gram, you get very stable images that are reproducible. If you are not, you have a problem with your technique and you should work with your applications person to, improve your technique.

We've shown that our, our initial results are reproducible at multiple sites. We believe that the sensitivity and specificity of compression elastography are greater than 98% sensitivity and approximately, in the mid 80% specificity just based on size measurements alone.

I think that since we've done these studies, we've learned more and are making less mistakes. And that our sensi, our specificity, is now probably in the low nineties.

This technique actually only adds a few minutes to the study can be interpreted immediately and guide you into, what you're gonna tell the patient. In our situation. We biopsy the patient while they're there. And again, this, really speeds up, our treatment of the patient.

We feel that the technique, really has the potential to eliminate a large number of biopsies. And it's better to say probably that this technique allows us to select which lesions really need to be biopsy. I think we can eliminate a lot of the biopsies we're doing on benign lesions presently with this technique.

I think that the combination of compression, elastography and ShearWave technology are gonna compliment each other, and actually improve the already very high sensitivities and specificities of this technique in breast.

I obviously don't recommend that you stop doing biopsies as soon as you get your elasticity imaging, system. You really need to, monitor your work and make sure you're getting accurate results before you stop, doing biopsies.

And again, the bullseye appearance I think is, very helpful in determining something is a benign, simple or complicated cyst. We find it very helpful, in helping us determine, how to do a biopsy an FNA versus a core, or just to, follow the patient.

Keith, key things, if you're going to use the size criteria, you need to see the lesion well on both B mode and the elasticity imaging. If you do not, then you really should not use this technique. You can use as the lesion harder or soft compared to other tissues to help guide you.

And the additional information we've talked about, screening is not yet possible. But there is no, reason why if we can improve these techniques to be, 3D, especially with ShearWave, where we get an absolute measurement that we could use these techniques in doing screening. And I think that is going to come, but will require, some time to get to that point.

Remember that elasticity imaging is really in its infancy. It's gonna continue to grow and evolve and, improve. There's no question that I think it's going to play a significant role in breast imaging and will eventually be added to the birad scoring system.

Work in other organs is going on, but again, just based on the, information we have on other organs, in vitro, it's unlikely that we're going to get as good of results we see in breast. But this technique will provide us some additional information that in some cases, will be very helpful in, diagnosis of, patients.

I kinda look at it in other organs, it's gonna be like color doppler. Sometimes it helps and sometimes it doesn't.

I thank you for your time.