Thank you, everybody, for coming to our session. My name is Margarita Revzin. I'm one of the associate professors at Yale Radiology, and our session today is going to be very comprehensive, very interactive. We'll discuss MRI and ultrasound, elastography, where do we stand. We have fantastic speakers for you, and everyone will have some questions to answer. Each speaker will take a turn, and at the end, we will have some time for you guys to also ask questions if you have any, okay? I wanted to introduce our speakers. We have Dr. Richard Ammon, a professor of radiology in Mayo Clinic. We have Dr. Vito Cantisani, associate professor in radiology at University of Sapienza di Roma, and we have Dr. Ronald Adler, professor of radiology at Langone Medical Center NYU, and we have Mira Tatyanovic, a professor of radiology at University of New Mexico and Arizona, and the last speaker is Arunak Kalipaka from Ohio State University. So I'm going to be right now asking the questions, and each speaker will have opportunity to come and discuss them. So the first question is for Dr. Ammon. Could you please share with the audience the physics behind the MR elastography described in commercially available regulatory-approved methods, and how do these methods differ in function and what they measure? All right, thank you. Thank you very much. I think this is an interesting session. We're going to be talking about various forms of elastography. We'll start here with MR elastography, and I can just say that from a physics basis, the way that we measure tissue stiffness with MRE is by using shear waves. Now that's widely used. It's what's used in many forms of ultrasound elastography as well, and it's based simply on the fact that when you put these waves we call shear waves, which are not sound waves, they travel much more slowly than sound waves, into by creating, by applying vibrations to tissue, these waves reflect the underlying mechanical properties. They propagate more rapidly in stiff material and more slowly in soft material, as you can see here. And if we then put continuous waves in, and that's what we use with MR elastography, that's reflected in the wavelength as well. So the wavelength is longer in stiffer material and shorter in softer material. That's the basic physical principle that is used to measure stiffness, tissue stiffness, with imaging. And the way that MR elastography works is that we apply, in its most common application, which is in the liver, we apply mechanical waves to the liver with a drum-like device that's pressed against the abdominal wall, and typically the waves are at 60 hertz, and those waves are then imaged with a special MR sequence that's capable of seeing these very, very tiny motions as these waves propagate through the tissue. So those are actual waves imaged within, that are only a few microns in amplitude as they propagate through the tissues in the upper abdomen. That acquisition takes about 15 seconds. It's done in a breath hold, and then automatically after the scan is over, the scanner computes the stiffness of the tissues in this cross-section, as you can see here. We call that an elastogram. So that's the basic way that MR elastography is performed and the basic physics behind it. What does it measure? There are many different ways to express tissue stiffness. In the case of MR elastography, it's something called the magnitude of the complex shear modulus. This very rich dataset that we have with MR elastography allows us to calculate both the real part of the complex shear modulus, which is the elasticity, and the imaginary part, which is the viscosity of tissue. And so it's the sum of those two, the geometric sum of those two, that is expressed as the stiffness in MR elastography. So that's the standard definition of stiffness. Now, you're aware there are other ways that stiffness can be expressed in terms of wave speed. Typically, stiffness is roughly the square of wave speed, and you can express it in terms of Young's modulus, which is roughly three times that of the shear modulus. But in any case, in MRE, it's standardized to be the magnitude of the complex shear modulus. And a key goal, as this technology was rolled out since 2007, has been to make sure that all of the manufacturers implement this technology in the same way so that the numbers can be compared across different manufacturers. So they use a common driver system. It's the same algorithm for calculating stiffness, the same value, the same definition of stiffness, the same frequency, and so on, same color scale, and other things as well. There's now a standardized protocol for performing an internationally recognized standardized protocol from Kiba, the Quantitative Imaging Biomarkers Alliance of the RSNA, which has a standardized protocol for performing MRE. And if you perform it in this way, then it reaches a certain level of performance that's described in this particular document. So you can download this. This is called Stage 3, and it's the first quantitative MRI biomarker that has reached this stage of standardization in the world. And my final slide in answer to this question is just to say that in a moment I'll be talking more about it, but the main application is in liver fibrosis. Acquisition time, about one minute. It's been FDA cleared and available commercially since 2009. It has its own CPT code. And if anybody tells you that MRE is expensive, it's incorrect. MRE, the reimbursement for MRE in the US is $220, comparable to many ultrasound examinations. So and it's been installed globally at 2,500 locations. And at Mayo Clinic, it's a common exam. It's about 43,000 MRE exams of the liver have been performed at Mayo Clinic since in the last 15 years. So I'll stop there. So could you please discuss the current commonly used applications of MRI-based elastography that are supported right now by published evidence and recommended as a standard of care? And which applications do you think are on the verge of becoming standard and which others have a really great promise? Thank you. So the most common and the standard application of MRE is in chronic liver disease. And it's basically to assess, detect the presence of liver fibrosis. As you know, liver fibrosis typically doesn't cause any anatomic change. So conventional imaging doesn't typically allow us to detect this disease. And we've seen now we've learned that we used to think in as radiologists, we could always detect even we could certainly detect cirrhosis by anatomic change. We've learned that that's not the case. So here are two patients with chronic liver disease. You can't tell by looking at these anatomic images if they have chronic liver disease if they have fibrosis. This patient has normal liver stiffness. And this other patient who had normal anatomy has a stiffness of three times normal and has advanced end-stage liver disease, stage four fibrosis. So this is the standard application of this technology. Here are 10 different exams. These are normal patients here. And here are eight patients who have increasing stages of liver fibrosis from F1 to F4, F4 being cirrhosis and F1 being mild minimal fibrosis. One of the most recent studies that has looked at the diagnostic performance of MRE is shown here. This was an individual data analysis, a meta-analysis that really looked at eight international cohorts, Europe, North America, Asia, and really about nearly 800 patients. And these are the cutoffs that were found for stiffness in sheer stiffness with MRE for various stages of fibrosis, as you can see here. And here is the diagnostic performance as recognized by the area under the ROC curve. And you can see it's very, very high. In fact, it's as high as you can possibly get given the uncertainty in biopsy. And I'll talk about that in a moment. So really, you can't probably do any better than that because the gold standard is imperfect. So it does excellent performance in diagnosing liver fibrosis. It's not affected by liver steatosis in any way, and it's not affected by body mass index. So this is an important issue with patients with fatty liver disease. Now, there's a sense that this session is a face-off between MRE and ultrasound elastography. I absolutely reject that. As a radiologist, I love having multiple modalities. We use the best tool we have available under the circumstances for a given patient. And the only exception to that might be in the case of VCTE, which is transient elastography, which is not typically in the hands of radiologists. It's a self-referral type of ultrasound held by non-radiologists. And so I do feel a certain level of freedom to comment negatively about that. And so what can I say about VCTE? So this is probably the most commonly available form of ultrasound elastography around the world. And this measures the stiffness of tissue about eight, six centimeters below the skin surface at a spot in space, as you see there. They take 10 measurements, and they decide how close they are. And that's the quality of the measurement. With MRE, we get a much larger look at the liver over a much larger volume of liver tissue. And that brings up the issue of sampling error. So you can see how if you measured stiffness in those two different areas with a spot measuring device, you would get a different measurement of liver fibrosis. Liver fibrosis is not homogeneous. So that's probably why consistently studies have shown that MRE performs better certainly than transient elastography. Now, this is becoming very important now because of the emergence of new drugs to treat this very common disease, fatty liver disease, which affects about one in three in the global population. And now as of March of this year in the US, there's the first of a new class of drugs that have been approved to treat this condition. It was big news when it came out. But one of the important points is that to be on this drug is $47,000 a year in expense. Very, very expensive. So we better get the diagnosis correct. And it turns out that really this drug is really at the moment only recommended with people who have F2 to F3 fibrosis, not F4 cirrhosis where it may not do any good, and F1 where lifestyle changes are probably recommended. So getting it right is very important. This shows current US payer requirements for coverage of a number of different covering agencies. Two of them do require biopsy, which I think is wrong minded because of course the sampling error problem with biopsy, it's really should be changed and it probably will be changed. All the rest will allow non-invasive qualification for this drug, this very, very expensive drug. Some of them allow blood tests, Pro-C3 and the ELF test for liver fibrosis. A lot of them will recognize VCTE in spite of the fact that it's actually got some problems in this area. All of them now recognize MRE as a way of qualifying and probably the most accurate way of qualifying these patients. So there are many other applications, potential applications, you'll be hearing more about them later. I'm going to mention the most important emerging application, which is in brain disease. So the simple application of MRE is in this situation. This patient has a pituitary adenoma, a very large one, and there is a very elegant way of resecting it called transphenoidal resection, which is a very limited type of resection. You can go home the next day after having brain surgery with this, but you can see that operating in this way, this tumor needs to be very soft in order to be able to maneuver it around to remove it in this way. We can now measure with MRE the stiffness of this tumor and should see in this case that it's very soft. Unfortunately, about 1 in 15 times these tumors turned out to be too stiff to remove this way and the surgeon has no way of knowing in advance until now. This, for instance, is an example of a tumor that's extremely stiff and would be very difficult to remove in this way. This patient needs a craniotomy instead. Another application of this technology and why it's coming in is it seems to be very powerful in assessing neurodegenerative disease. Now, again, these particular applications would be inaccessible to ultrasound, so I think they're important. You can see here how there's this dramatic decrease in stiffness in this patient with Alzheimer's disease and the convexities of the brain compared with a normal age-matched normal. It turns out that many forms of dementia, neurodegenerative disease, cause the brain to become softer, which is an important finding. In fact, the changes are so striking that they can actually be recognized regionally, and we think this will be increasingly used in the future. But here's the last thing I'm going to show, which I think is really an important emerging application of this technology in neuroimaging, and that's assessing something called normal pressure hydrocephalus. This is one of the conditions that causes dementia, and it's the one condition that's now treatable. So normally, it's associated with enlarged ventricles, which can be due to atrophy or could be due to very slight increased intracranial pressure. Symptoms are very similar to those of Alzheimer's disease, and it's very difficult to discriminate between them. It's not uncommon, 2% of patients 65 to 80 and 8% of people who are 80 and over. So this is not an uncommon disease and a cause of dementia that is reversible, and the reversible ability is based on doing shunt surgery, which has a success rate of 75%. But it's very difficult to identify those patients who have this condition versus those who simply have other forms of dementia. We have now seen that there's a signature that's very characteristic in the stiffness in these patients. There's also something called damping ratio, and we can now separate out. Here you can see this group in red who have the condition, normal pressure hydrocephalus, and patients who are cognitively normal, and those who have Alzheimer's disease, beautiful separation between them. It's a very strong signal, and this will, we think, will be used widely in the future. Just to show you one additional slide before I wrap it up here, to say, you might say, okay, well, show me that this actually changes, that if you treat the patient, that this actually gets better, that these biomarkers that we see here that are abnormal go towards normal. And we have had that opportunity here, and other people, other researchers, this is a patient, these are a number of patients before treatment, and then they got shunted, and here's what happened after they were shunted. They all went back towards the normal range. So this is a very important emerging application, one example of where this is going. So wrapping it up, this is a standardized MRE technology. It's widely deployed worldwide. It's an important part of our diagnostic armamentarium of one of the elastography techniques that we should have available to us in radiology and most places. It's a reliable way of assessing liver fibrosis. Brain imaging will be the next widely used clinical application, and there are many other applications that are being explored. Briefly describe the physics principles of ultrasound elastography, as well as share your perspectives on the use of ultrasound versus MR for evaluation of liver stiffness. Thank you. What are the pros and cons? Thank you. Thank you so much, Margarita. And yeah, we are entering in a controversial and very hot issue. Ultrasound or MRI, or both, most probably. Firstly, we start from what is the prerequisites. To do a right ultrasound elastography examination, you have to follow the indications that are not for any patients. You have to be adequately trained. You have to instruct patients to follow you. That is different than when you do also other stuff. Then you have to follow the suitable parameters, follow guidelines, and avoid some artifacts that can influence negatively your examination. I suggest you to read a very short paper that we published together with an hepatologist, Fabio Piscaglia, with whom we are really working these years, trying to put transient elastography that was referred by who talked before me. And right now, the point shear wave and 2D shear wave. Secondly, I show you how you have to reach the right evaluation. You have to avoid artifacts that have to be perpendicular to the capsule, one to two centimeters below the capsule. And then the ROI, following some qualitative indicator that helps you to really obtain the right shear wave. Shear wave in ultrasound works similarly to MRI, but they reproduce color map as MRI, and they give you an evaluation of stiffness that is really reliable as well. Now let's try to enter in the clinical work. If I have a patient with a liver lesion, do I use ultrasound elastography? The answer is not. There is no evidence, and we did not recommend in our guidelines, and in our paper, we show that is too much overlap. Let's see some example. Typical stiff lesion. This was a MET. But conversely, another lesion that was stiff, again at a shear wave, and this was a cavernous hemangioma. Another lesion, and this was intermediate stiff, and this was ACC. Therefore, we cannot suggest to use in this kind of patients. What about chronic hepatitis and patient with steatosis? In this very nice paper that I suggest you to read from Guglielmo and others, they put together MRI and elastography, and they show that we need to use both of them to reduce the number of biopsy. Again, again, another important element, cutoff values. As I showed in MRI, there is a very strict cutoff value, 2.2, 3.7, 4.4. Then we decided to simplify, and we obtained a new recommendation that I show you now, and we use them for sure to exclude significant fibrosis, and diagnose cirrhosis in patients with chronic hepatitis B and C. We are following also some important influences from the techniques and from the patients that you have to follow, both for MRI and for ultrasound elastography. What is important right now, we have a quality indicator that helps you to do a real-time evaluation. We are reducing the number of measurements from 10 that was in the past for transient elastography to five, even to three, to simplify the process and to obtain better results. Now what are the challenges and what are the advantages and disadvantages? Of course, as already proved, MRI elastography, when it is really properly performed, when you have the proper MRI, then you can obtain very accurate results. But on the other side, how much does it cost? And if you do screening, and if you have to follow this kind of patient every six months for five years, how many MRIs you have to do? They are full ultrasound, as right now, not transient elastography, but ultrasound elastography, good reproducibility, prove it, and it could be suitable for surveillance. Unfortunately, still we have some problems to discriminate hepatoinflammatory changes. And this is one of the limitations we have right now for this kind of examination. And I put here again, all the possibility and also another important field where I use ultrasound elastography is a patient that cannot be submitted to MRI, claustrophobic, metallic artifacts and whatever. Let's see this example, typical cirrhotic patient already, but you need to include the patient for the treatment. And then we have the evaluation, the number, the qualitative indicator that show you that this is reliable. And also in this patient, I depict also this lesion. Then I tried with color doper, color flow, with elasto, elasto did not work too much. I told you already it was intermediate stiffness, but to look at CUS, if you include CUS, you can obtain the diagnosis. This is a proven cirrhotic patient plus hepatocellular carcinoma with multimodality evaluation. What about fat? This is really the field in which we are really evaluating our patient with ultrasound, new fat fraction evaluation. This is an example at baseline, it looked like mild, moderate, stratotic patient. Then we did our evaluation. This is the number of ultrasound and the number of MRI. Very similar and comparable. Both of them stated normal patient. Again, another case. In this case, again, the number are very similar and this is a moderate stratotic patient. But now we need to put together and we can do with some typical new techniques and we can evaluate, as in this case, severe stratosis at baseline. Then we prove it with fat fraction and in addition, we do also ultrasound elastography. And at the end, we can conclude that this is a severe stratotic patient with compensated associated chronic liver disease. Future. Well, in this paper, they summarize some possible emerging trends and integration that I suggest to look for, because this could be the solution to put together, especially in the three key cases, both the technique, AI, new power diagnostics, that helps for sure, hybrid approach. And also we are really shifting to non-invasive evaluation. Therefore, I summarize it for you, what are really the established role, hepatic complication viruses, for sure we can investigate. Still, we cannot use this kind of examination for the characterization of liver lesion. What about other organs? Few words, starting from spleen. What it is really nowadays established, we can use to monitor dynamic changes in portal hypertension in order to predict non-invasively the viruses progression or the good answer to the treatment. What about the other organs? Kidney, just few words. We can do bold MRI. We can do photoacoustic imaging, elastography and diffusion MRI. And recently, this very interesting paper compared MRI and ultrasound, and they show that if we go through the multimodality evaluation, we can achieve similar results, not really the same one, but similar results that in this kind of setting is really important. Okay, so basically, we're going to briefly describe what elasticity imaging is from an ultrasound standpoint and go through some basics in the next few minutes. So basically, it allows us to display a response to soft tissue from an external perturbation or deformation. So historically, what we think of as ultrasound elastography is what we call remote palpation or compression-based elastography when you apply a transducer to the soft tissues and apply a low amplitude perturbation or deformation of the soft tissues so that we can take a lesion such as indicated on the left here and ascribe a new type of contrast to it based on its relative hardness in terms of its strain. And that's indicated in this image over here on a sort of conventional rainbow image. But with shear wave elastography, as you've seen in the last few minutes, is that we can actually make this a quantitative method where we actually extract the functional information as well as pathologic information in terms of physiologic parameters that we can actually determine directly. And this basically has to do with an inherent assumption that's always made, is that we're assuming that all soft tissues are linear, isotropic, homogeneous, and incompressible. And so that if we apply a longitudinal deformation to the tissue, that deformation, the stress on that soft tissue is linearly related to the deformation or the strain through an elastic coefficient that we saw before. This case, it's a Young's modulus. If we apply a transverse deformation, then again, the stress is related to the transverse deformation through the shear elastic modulus. And these two can be related through a simple relationship indicated here, where nu is the Poisson ratio. And for incompressible soft tissues, which is one of our inherent assumptions, is actually a very good approximation. Nu actually has a specific value, in which case we see that the Young's and the elastic modulus are related through a very simple relationship. Now the other thing to recognize is that we used a feature that we used to find disconcerting, namely speckle in the image. And for a long time, we tried to develop methods to reduce speckle to make our images look more anatomic. We know speckle can be very useful because we use it in extended field of view imaging that basically takes a small field of view image and makes it into as much as 60 centimeters worth of information. But the important feature here is we can use speckle to detect changes both spatially, both in location and in time. And therefore, we can actually use it to get a strain estimator as well as to track shear wave motion. Just to show you that there has been a lot of work in the last 30 years in terms of ultrasound techniques to display various elasticity, to display elasticity information, this gives you an idea of various elastic graphic techniques that have been developed using ultrasound. We're going to concentrate on two, namely strain imaging or quasi-elastic strain imaging or compression-based elastography, it all has the same name, and shear wave imaging. We'll start out with quasi-elastic strain imaging. And basically what we're looking at is we're going to do speckle tracking as a strain estimator. So we apply a superficial deformation to the surface using a transducer, usually at very low frequency, try to keep it very small amplitude, something on the order of 1% to 2%. And we use speckle tracking to help calculate the deformation. And what we hope to do is be able to take information such as a lesion that's basically iso-echoic to the adjacent parenchyma, as in this phantom over here, to show that it in fact shows high contrast based on its strain properties, namely this has very low strain relative to the adjacent soft tissue. And many of you, as I showed before, are familiar with the so-called rainbow display where blue is assigned the low strain and softer adjacent soft tissues goes to green, yellow, and red hues as indicated here. Now basically this illustrates the basic physics. We're looking at the time domain here and we apply a small compression and we're looking at speckle within that A line of data and we're using a correlation technique in order to calculate the displacement and transform that into a displacement or a strain map that we can then subsequently assign to a 2D parametric image as indicated over here. And basically since we're assuming that stress across the soft tissue is really constant, you can see that the strain is actually inversely related to the elastic modulus. So we can actually see that relationship, the strain map basically gives us an indirect measure of the elasticity within the soft tissue at any point. Now there are a number of advantages to using strain. Of course it's easy to use. It's a high spatial resolution. It's real time. There are a number of features that are very attractive to it. However, the one disadvantage that I would emphasize is that it's highly subjective. It's very operator dependent as you can imagine. So no two people doing it may get the same results depending on how they perform. So we want something that's a little bit more quantitatively reliable. So that takes us to the next area, which is shear wave imaging, of which there are two types. One of which you've seen a moment ago, which is transit elastography, where you have an external device producing a periodic compression, which is low amplitude, relatively low frequency. And we're looking at the subsequently produced longitudinal shear wave. And we're going to use either speckle tracking or we're going to use tissue Doppler techniques in order to calculate the phase propagation as a function of depth, from which we can, based on the depth and the specific phase delay, that we can calculate the shear wave speed, which as was shown before, directly relates to the shear elastic modulus G. This is generally a quantitative technique. It's the same thing that's used in the liver in the FibroScan, although it can theoretically be made into an imaging technique. Now the area that becomes more exciting certainly is using acoustic radiation force imaging and where the transducer actually produces a push pulse that results in a momentum transfer to the soft tissue and sort of indicates on the parameters here. And then the tissue responses, since it's linear and isotropic, the wave that gets produced is basically a solution of the wave equation, which I've indicated over here, and appears as a transverse wave going perpendicular to the direction of the applied shear wave, the applied push pulse. And then we use the transducer then to send out a series of tracker pulses in order to track the subsequent displacement field as a function of time. So this is basically what this would look like. This comes out of Dr. Toyanovich's article, where we have the transducer producing the push pulse, and then we go into an acquisition mode where we're going to use tracker pulses, for instance, in order to look at the propagation of the shear wave. And then once we calculate the velocities, we can convert that into a parametric map, either in terms of tissue speed or velocity, shear wave velocity. Or using this relationship over here, we can actually produce a parametric image of Young's modulus or shear elastic modulus. So that's ultimately what we're going to do when we produce these images. So here's an example. This is a normal muscle over here. This is our parametric map of shear wave velocity. We also produce a quality map, which is sort of a goodness of fit, if you will, based on correlation coefficients, as well as a signal-to-noise ratio from the quality of the shear waves that we're producing. And then we can take sample volumes within this, as indicated over here, about two or three millimeters in dimension, which we can calculate the shear waves at two different points, and we can calculate the time, peak-to-peak time, from which we can extract the shear wave velocity. Okay, there are a number of advantages and disadvantages. I think probably the fact that it's quantitative is probably the single most important advantage, because we're actually measuring directly a physiologic parameter. Probably the greatest disadvantage, since you're producing waves in general, and you have to deal with all the issues that have to do with wave propagation. So you can have reflection artifacts at various interfaces. You can have refraction artifacts. So basically, since most tissues are inhomogeneous, particularly musculoskeletal tissues, that can potentially pose a problem. And then one of the other disadvantages is that it assumes that there's a given direction of propagation when you apply the shear wave technology. So with regard to the musculoskeletal system in general, one of the issues that we have to deal with is tendons and muscles are neither homogeneous nor isotropic. There are certainly issues regarding the transducer in general. One thing we haven't really touched upon, but the fact that most tissues actually have viscoelastic response. So that the shear wave speed that we get actually is a frequency-dependent quantity, so that higher frequencies, in fact, are highly attenuated. So that's why you really want to go lower frequency regime, ideally. And then, as I mentioned before, this assumes always a given wave, a given direction of propagation, but we know muscles and tendons can be highly anisotropic. So that there may be another preferred direction of wave propagation that we're not appreciating. We can pass this, since I spoke about quality maps. This is just some validation data. There are certainly a number of articles out there. But this is taken out of the University of Wisconsin group, where we looked at four separate muscle specimens, where they're measuring, it's measured shear elastic modulus, or Young's modulus versus the calculated from the shear wave on four different specimens. And you can see there's a high degree of correlation between the measured and calculated values. Dear colleagues, as you know, ultrasound shear vellistography is an emerging technology. And that can be used as an extended tool to grayscale and Doppler imaging in the evaluation of various traumatic, pathologic, and postoperative conditions of the tendons, muscles, ligaments, nerves, joints, and other soft tissues. At the present time, there are many applications, but we cannot still distinguish between benign and malignant tumors. So since I published this paper in 2017, it was cited numerous times. And I did literature search in PubMed between January 1980 and January 25. And I found 334 papers on shear vellistography of the tendon, 1,057 of muscle, 90 of ligament, positions of tissue tumors on the seven, several on arthritis, and several on nerve, including 46 on carpal tunnel, nine in last year. So this meta-analysis by Albano et al. included 16 studies with 676 pathologic tendons and 723 control tendons. And the authors concluded that pathological tendons may have reduced shear vellocity compared to controls. But the evidence is very uncertain, and future studies are needed. This is a promising paper with promising results on evaluation of post-operative Achilles tendon. And the authors evaluated the tendon at 12, 24, and 48 weeks post-operatively. That is studied by Gilolo et al. And the authors concluded that Achilles tendon seems to become stiffer with the healing process. This meta-analysis on rotator cuff by Set et al. included 16 studies with 520 patients. And the authors concluded that shear vellistography of the supraspinatus tendon can be a useful diagnostic tool for the orthopedic surgeon that provide quantitative information of tenderopathic stiffness, velocity, fatty infiltrate, and elasticity characteristics. Here is a nice pilot study by Nocera et al. which suggests a temporal relationship of MRI and ultrasound parameters that parallels the expected phases of healing in the repaired rotator cuff. So, the tendons became stiffer as they healed after six months. Ultrasound elastography is used very much in the evaluation of plantar fascia. And this meta-analysis by Wu et al. included 11 studies. And the authors concluded that plantar fascia were less stiff in plantar fasciitis group than in asymptomatic subjects. This was confirmed in this nice paper by Bauer et al. And this study included 108 unilateral plantar fascia, including 87 patients with plantar fasciitis and 21 asymptomatic individuals. And the authors concluded that shave elastography allows quantitative assessment of plantar fascia stiffness, which decreases in patients with plantar fasciitis. However, no correlation to the thickness of the plantar fascia was found. Meta-analysis on ultrasound elastography of back muscle biomechanical properties by David et al. included 79 studies. And the authors concluded, while still in its early stage, exploration phase, MSK ultrasound elastography may reliably quantify back muscle biomechanics in asymptomatic individuals and more. So, shave elastography is very useful in evaluation of muscular dystrophy. And there are several patient papers published. And I'm just showing this one on Harada et al. In children with Fukuyama muscular dystrophy, the authors evaluate several upper extremity muscles and concluded that muscle in patients with this disease were atrophic and became more atrophic with increased stiffness in older children. Paper by Zhang et al. evaluated coracohumeral ligament in patients with different stages of adhesive capsulitis, and the authors concluded that coracohumeral ligament stiffness of the affected side and its correlation with the shoulder vas analogue scale score and range of motion are different for different stages of frozen shoulder. A lot of studies on carpal tunnel, and this is one of them by Cernik et al., Skeletal Radiology 23, and the authors concluded that median nerve shear wave velocity and stiffness are significantly higher in carpal tunnel syndrome patients, and that this modality can be used to diagnose carpal tunnel syndrome and distinguish between patients with mild and severe disease. So these are a couple of cases from my practice, and we can notice the difference between malignant and benign tumors. On the right is a patient with endothelial rheumatosis, and you can see very hard consistency of the tumor. So this paper on evaluation of soft tissue masses by Wien et al. included 150 bad consecutive patients, 87 benign and 60 bad with malignant tumors, and the conclusion was the strongest predictors of malignancy are large lesion size and high vascularity. The combination of all ultrasound characteristics, including shear wave elastography and MRI features does not confidently classify lesion as benign or malignant, and histological diagnosis remains the gold standard. So in conclusion, shear wave elastography is an emerging promising tool that may complement the diagnosis obtained by grayscale and Doppler imaging by quantifying mechanical and viscoelastic tissue properties. In current clinical practice, this modality may be used as an extended tool in ultrasound evaluation of tendons, muscles, ligaments, and nerves. Emerging research in MSK shear wave elastography is rapidly increasing its clinical applications. And I'm going to ask Dr. Aruna Kalipaka to come to the podium and discuss this, if he can provide some insights on the current status of these applications, and when would you recommend using the elastography in this context, and what benefits might it offer to radiology? Thank you. Some challenges. Thank you. Thank you, everyone. Just as Dr. Eman has already mentioned about how elastography was and the future applications, I would like to briefly go on with the different applications right now, where the potentials are and what can be done in using MR elastography. So first, I would like to showcase how breast MR elastography is being done. And as you can see, a subject is laid into the scanner by having the breast lying down so that it doesn't get compressed, and you have a sternal driver. As you can see from here, this driver doesn't touch the breast, but from the sternum, you can have the waves propagating into the breast. And as you can see here, beautifully the waves propagating. And for example, I would like to showcase an example here where it's a grade 1 carcinoma, and you can see that the stiffness is different compared to stage 3 carcinoma, where the stiffness is a little bit higher. So this is one of the potential applications. But the major challenge in having a breast MR elastography is you don't want the driver touching the breast, because you don't want it to be compressed. When it is compressed, that can cause potential problems in terms of how waves are propagating, and it can lead to biased stiffness estimates. So that is one of the potential problems. So you have to create a soft sternal driver that can send the waves in. Then the other potential application I wanted to show you is lung MR elastography. Actually, as you already know, in lungs, the amount of parenchyma is very less, and it is filled with air, and MRI does not give any signal, mostly, as you can know. But we can do MR elastography with having beautiful waves propagating even in the lungs. As you can see, here is an example with when residual volume versus total lung capacity, the waves are a little longer in total lung capacity, and it is stiffer as it is filled with air and the tissue is stretched so that it has longer waves going into the region of interest. And as you can see, at total lung capacity, the stiffness is higher. And the other application I would like to show you in lungs is cystic fibrosis. And this is in cystic fibrosis, as you have the mucous accumulation in the lungs, and you can see the waves are getting longer, and you can easily estimate the stiffness in cystic fibrosis, showing the higher stiffness estimates compared to the normal are healthy. And this is an intermediate pulmonary nodule. As you can see here, MR elastography is performed, and we can even go ahead and estimate the stiffness of the pulmonary nodules, which are very important because most of the times you go and do a biopsy, which is more challenging. And this can potentially provide some information, but there are a little more challenges when applying MR elastography in the lungs because the signal is very low, and we need to make sure that you have sufficient signal and the phase SNR is at a certain level in order to calculate the stiffness. And the other application I would like to show you is cardiac MR elastography. And as the driver application is the same, you put a driver on the chest wall and send the waves in. And here is an example showing in a hypertrophic cardiomyopathy. This is one of the applications, but there are many applications. Typically diameter is used as a, sorry, the thickness of the wall is used as a criteria to estimate, to go and diagnose this hypertrophic cardiomyopathies, but in most of the athletes, if you can see, they would have a thicker wall. That doesn't mean they have a hypertrophic cardiomyopathy, but in those cases you can apply this technology and estimate the stiffness to determine if the tissue is normal. And here are some examples showing you the stiffness variations between a hypertrophic cardiomyopathy versus normal healthy subjects. And the other potential application is aortic MRE. Right now there are many applications in aortic MRE. For example, you can go and look at the dissections as well as aneurysms and also hypertension because the aorta gets stiffer with hypertension as well. But in aneurysms and dissections, you can go and characterize using the stiffness. But the important challenge here is in aorta, you don't have that much spatial resolution, so we use both the wall and the lumen in order to observe the vibrations in the whole aorta and estimate the stiffness. As you can see here, here is an aneurysm, which is around five centimeter diameter, and you can easily estimate the stiffness of this aneurysm, as you can see, and the transition zone is a little bit stiffer, whereas the remote zone is a little softer. And here is an example showing you why you wanted to use stiffness in order to characterize the aneurysms, because here are examples of aneurysms with the same diameters. And as you can see, in this case, the aneurysm is a lot stiffer, whereas in this case, with the same diameter, the aneurysm is softer. And I would say this aneurysm is more prone to rupture because the other area of the aorta is a lot stiffer, but whereas this aneurysm is a lot stiffer, so sometimes patients who are above a certain age, you don't want to go and operate as long as the aneurysm is stiff and stable. So that way, they can even avoid some medical treatment or endovascular aneurysm repair if it is not needed. And here is another application, as you can go and estimate the stiffness, where you can estimate the stiffness and also wall shear stress. Wall shear stress is estimated using the 4D flow MRI, and that compared to the stiffness measurement. As you can see, there is an inverse correlation to stiffness versus the wall shear stress. And I would like to show you some applications, even in the lumbar spine. As you can see here, you can send beautiful waves in the discs and estimate the stiffness of the discs as well. Where are the potential applications? Right now, firmament grading is being used to characterize the discs, where they wanted to see at what stage of firmament grading is and compare it to the shear stiffness. As we can see, with the increase in the firmament grading, the stiffness also increases. Because this is one way to look at the disc degeneration and the biomechanical properties of the discs, which are very crucial for someone with low back pain. And the other application where you can apply MRI is if you have an internal disc ruptures, as where if they are getting operated or needs to be operated, as you can see with the octahedral shear strain, you can go and differentiate the disc that has had a fracture versus non-fractured disc. So that way, this MRI has potential of a lot of these applications. And I haven't shown the other applications also. For example, in kidneys, it can be applied in the kidneys. It can be applied in the spleen, as well as in other muscle areas. So a prostate, pancreas. So there are a lot of other applications which has potential for using MRI elastography. And with this, I would like to thank you. Thank you very much. That was very interesting. Thank you. I wanted to ask Dr. Contestani to come for just a few minutes to talk a little bit about some promise that we have for ultrasound, elastography, and evaluation of thyroid nodules and salivary gland pathologies. It's something that we really look forward to. Thanks a lot, Margarita, for giving me again the possibility to address another very hot issue. Thyroid nodule. What is the real problem? Every day, we identify a nodule everywhere, to everyone. Therefore, what is needed is to reduce the overdiagnosis and overtreatment. We have established some specific worrisome signs that we encounter every day when we do this kind of examination. It is clear when we found this lesion, we found the possibility to depict the colloid appearance. It is clearly benign lesion. When we found is another lesion with the hollow side, it is very regular, very, very, very high-strike lesion. There is no worrisome about it. But of course, when we encounter microcalcification, irregularity of the margins, hypoecogenicity compared with the muscle, taller than wide appearance, mostly applicable for breast cancer, but also possibly applicable also for papillary cancer. And of course, if you put together, you find this lesion, taller than wide, irregular, and invasive on the capsule. This is a typical sign of malignancy, but however, there is no single sign that is enough accurate to make final diagnosis. Then we try to group together all the single features in order to provide the tie-dots. But unfortunately, we are like Moong looking at his wonderful masterpiece because we still don't know which one to use and how much is the inter-observer variability. Therefore, we tried to enter in this field, elastography, strain, shear wave. Right now, we know exactly that 2D shear wave is the most used for liver, as I showed you, but also for thyroid, also for breast, also for MSK as was already proven. What we do every day? We evaluate nodule. We found these very stiff lesion. We found also that this lesion, before and after compression, can have a major size. And this is also a worrisome sign that is related with, unfortunately, a poor outcome. Then we do in the same case, shear wave, again, this is a stiff lesion. We can do single point, but then the problem is, should we do everything? Should we combine? Luckily, technology is helping us to have the possibility to combine both in real time to obtain faster and more complete evaluation. Therefore, we have these cases. This was a proven papillary cancer at ultrasound showed intermediate appearance. It was classified by someone as a type 3, others type 4. We measure, no worrisome size, no color flow, neither we use a 3D evaluation. Then we do strain. This is a stiff lesion. Strain ratio, look at the size, look at the ROI. Usually what is important is to put the ROI really in the internal part of the nodule and entire parenchyma, avoiding artifacts. Shear wave again confirms, but what is interesting in this case that I want to show you, if you apply a new possible probe that allow you to have the 3D representation, the margins are really better evaluated that these were really worrisome. What is present in the literature? We did several studies and I already introduced to you what is the problem. In China, Japan, Korea, we have some very promising results. Europe, very good promising results. States, controversial and not clearly favorable ultrasound elastography. In this paper that we did compared thyrads and then expert operator and beginner compared with strain, shear wave, we found that strain performed better and achieved a sensitivity increase of 10% compared with thyrads. Meta-analysis in the literature, this is one of the most updated, confirmed what I told you in a larger number of patients. And if you look at the guidelines, we stated that ultrasound elastography can be applied as an additional part, not substituting part of baseline. My idea and expert idea is not to downgrade the worrisome lesion at baseline, but to upgrade the one that is not worrisome at baseline, but it appears that it is stiff, reminding us that 10% of malignant nodules may be soft, but sometimes we are not able to depict the worrisome sign, especially in the follicular one. Then let's enter in the evaluation of what is controversial. Recently, this was published in Radiology and showed some expert opinion in which they stated elastography is not useful because it does not add anything to our baseline. On the other side, I suggest you to read this paper that will be published next month in the European Journal of the Sound. It is freely downloadable. We review all the features. We provide the educational part because what is really important to achieve a very good result is to be very well prepared. If you don't use it properly, you will never achieve good results, of course. And I summarize for you the conclusion and some advantages that for sure are very easily achievable if you follow the right protocol. Nowadays, we talk about multi-parametric ultrasound. As I showed before, MRI at the beginning was without contrast agent, then contrast agent was introduced, then spectroscopy, then elastography. Right now, do you do your MRI without all this software? The answer is not. And the same is appearing that is also important for ultrasound. And in this field, if you go together, all the people that they do really everyday cases and cases and cases, they have the idea that this is very helpful. Another important information, the new equipment have AI-based technology. Therefore, if you work more and properly and introduce the right scanning, you teach your equipment also to give you more feedbacks. So again, this is very important. And last but not the least, we are announcing that we are going to introduce the new guidelines in which we reviewed critically, but really based on a Delphi method to see really if there is evidence or not to state it works or not work. And not just based on my opinion, your opinion, because every one of us can have different opinion in the same day. So the challenge, still we have to face the problem. Any vendors, any equipment has a different cutoff. And this is really the Achilles tendon, for sure, the Achilles weak tendon that we have right now. Secondly, multiple nodule goiter. Right now, we have new technology that is helping us to have the possibility to reproduce elastography and the identification simultaneously. But for sure, the future is to integrate AI in our protocol. So I tried to summarize for you. And thank you so much. Thank you very much. Thank you. That was fantastic.

MRI elastography

ultrasound elastography

tissue stiffness

liver fibrosis

shear waves

diagnostic accuracy

standardized protocols

AI integration

medical applications