Role of Contrast-Enhanced Ultrasound in Radiology

I am professor Paul Todo from King's College in London, and I shall be the chairman for this session this afternoon. We have two lectures in this seminar sponsored by Bracco and Siemens Healthineers regarding the role of contrast enhanced ultrasound in radiology. It's important that we have some sort of concept of where we have come on the long journey with contrast enhanced ultrasound in radiology by just giving you a brief overview of some of the history of which I was involved with in the last 25 years. In the 60s, agitated saline was used as in echocardiography as the contrast agent, but it took quite a long time because of some slow technical limitations. But in the last 20 years or so we have seen an explosion in the development and discovery of acoustic patterns of microbubbles and a consolidation in both knowledge and practice microbubbles or contrast agents are really only licensed in a specific areas like the liver, heart, breasts or the peripheral. Vascular system but practitioners have started using it in all sorts of other areas, including the kidney, the pancreas, the altar, and the testes, and is now established worldwide in practice and recently also in the United States. It's worth remembering that these agents were first used, and by myself at Kings College Hospital in the late 1990s, looking at what was called Doppler Rescue, where you could not see a vessel on your B mode ultrasound examination, but adding the contrast agent would show this. You really very clearly, and in this case the portal vein and the hepatic artery in a pre transplant patient and this would have revolutionized the ability of using Doppler ultrasound with contrast agents. The agents be used then was Levis, which is no longer manufactured. We used it in other areas as well looking at the. Enhancement of the Apache Gartree pre and post contrast agents again using LUVIS to prevent unnecessary investigations in a patient who has had a recent transplant. And you could not see the app attic artery furthermore, and development occurred and with son of you coming on the market. We were looking at the patterns of vascularity with Doppler rescue in focal liver lesions. Looking at the pattern of that vascularity to see whether or not we could say this was. Lectin over benign lesion. A very observational, subjective assessment of bass clarity and a tumor. We also used it in the peripheral vascular system where again it was used as a Doppler rescue agent so you could see the the arteries a little bit better. This took a long time to do. Develop and to bring into clinical practice. But all of this changed in the early 2000s when these acoustic properties of the microbubbles were brought to the fore and we started using harmonic imaging, pulse inversion imaging and looking at the resonance of the microbubble looking at low mechanical index imaging and this completely changed the way we looked at our contrast. Contrast is very very safe and this paper out of Italy shows they were the reactions of very. Low 0. We've got an agent which we've gotten evolved from being a Doppler rescue. Too low mechanical index imaging looking at focal liver lesions with great accuracy, and this afternoon in our seminar, which is dedicated to the role of contrast enhanced ultrasound radiology. We have two eminent speakers, Professor Anders Nilsson from Sweden, who's going to show you how to optimize the use of your contrast enhanced ultrasound in your department and Professor Kenyan from Beijing. Who will talk about in more detail using contrast enhanced ultrasound in limit imaging and why? Contrast enhanced ultrasound should be the normal practice. I'm looking forward to both lectures and I'm sure you're going to learn a lot here over to the lectures. Thank you very much. Well, first of all, I'd like to thank the organizers for of this museum for inviting me and giving me a chance to come share my thoughts about why, why it seems to be so difficult to implement something that is so easy as contrast enhanced ultrasound in so many departments. First of all, just a brief reminder why we use contrast tool. These trees that I pass every day on my way to work. And as you can see there different types of trees. But it's so much easier to see that there are different types of trees when they have a different. There's a contrast between the coloring. And the same goes for imaging. It's easier to see that things are different tissues if there is a contrast in between them. So why should we not these when when we think about starting using contrast enhanced ultrasound? These things we get to hear it's expensive, dangerous, difficult, user dependent, still not good enough and time consuming. But if we just take a brief moment to go through each, is it expensive? It's not expensive compared to other contrast agents at all is a dangerous, very, extremely low toxicity. Allergic reactions are rare. They're on par with gather Linnean contrasts. Is it difficult now it's the same sort of ultrasound scanning that we've always done that come with with new criteria that are very easy to learn. Is it user dependent? Yes, but after after doing ultrasound for 30 years, I'm getting really tired of hearing that ultrasound is used dependent because really everything is user dependent. We need to know the modalities that we use in otherwise it doesn't work, so it's user dependent. Yes, but so so is everything else still not good enough. Well, we we're 2021 and we've been taught for many years now that we should be. We should be evidence based. What we do should be based on what's published and where, where ultrasound is inferior to other modalities. We should use other modalities, but when ultrasound is superior to other modalities with contrast many we we should use the contrast enhanced ultrasound. Is it time consuming? Not really. For me it actually saves time because if I'm looking for metastases, for example in in some of the patient groups. We routinely check for metastasis if I'm going to look for a metastasis on B mode image only, I'll I'll spend 20 minutes half an hour looking for a great doctor. Grants to grey background, whereas if I inject contrast, I'm looking for a dark dot has the right background, which is so much easier and so much faster. Quick reminder that when we do our sound contrast we send in a signal and the bubble starts resonating and the contrast bubbles send out a signal that is not quite the same as as signal that we sent in. So when we when we're giving contrast, we're we're making an image based only on contrast concentration. And this is. This is important because if we do the CT or MRI image then you have the basic image and that image is the contrast is enhanced by injecting something in ultrasound we're making. It's a deep, completely different way of creating an ultrasound image. 'cause we we build a new image based only on contrast concentration. This is an example where you see where there is there has been a pancreatic tumor here that we've done in IR, a microwave and my hiry ablation of and where the tumor was where we kill the tumor. There are no blood vessels in. If we use B mode ultrasound, there would be echoes in here, but now we're building the image only on on contrast concentration, and there where there is no contrast, there will be no signal, whereas blood vessels would be very bright to liver will be. Slightly less bright, but still. So remember this, it's a blood pool agent. Yeah, contrast can only be where blood vessels are and it it's still another. An ordinary ultrasound image. It's still a real time itself. Uh, in the arterial phase, the echogenicity will depend on vascularity, because we build the image in contrast concentration, so more vessels means more blood, more blood or blood means more contrast. More construct needs a brighter image. In the arterial statement in in, in the late phase, the ECHOGENICITY will be more dependent on tissue differences. Are there there sinusoids where where the contrast bubbles will be trapped? Is there a capillary bed or their tumor? The tumor vessels that will let the contrast through easily? Couple of examples why we should give ultrasound contrast three different categories, similar categories, but in the email Hemangioma group I try to cover like to call that boomerang diagnosis because if we say there's a hyperechoic lesion in the liver and it's consistent with the human genome and the patient will be back. Worst case scenario for an MRI and best case scenario for another exam taking out. More time to give contrasts to to confirm that it's a human German. Uh, the other two patients 64 year old male with cirrhosis and 38 year old woman query goldstones. I'll show them to you now. The first one is this one where where you have the cirrhotic patient? And you can see there's a hyperechoic lesion there. And if you look, take a moment to look through them. I put the question to when I'm giving a lecture. A while back I put the question to the to the participants. How many versions do you see? And this is the result. 5% so none. And I assume that they once had already fallen asleep from my lecture. And just pressed something in panic. Most people saw one couple sought, sought to, and I think the people who said they saw three. They probably saw two, but thought I'm trying to trick them so they added an extra one to be on the safe side. But most people in Lisle one lesion. And if you look with with contrast, you have that lesion enhancing in the arterial face up there. But there is another lesion down here and now that we know where it is we can see it on the B mode image as well, but I will have to admit that I didn't see it initially on the B mode image. I only saw it when we'd be given contrast because we had the other lesion. Up here but now that we know where it is, we can even follow it overtime and you see the late face wash out here meaning in the cirrhotic patient. This is in all likelihood NHCC, and it's important that we finally sees when they have this size, because this can be treated with percutaneous ablation easily. 38 year old woman and. She was referred from her GP Queer gallstones and when the exam was done, the guy doing she asked the guy doing Sam, do I have any gallstones? And the reply was no, you have no gallstones, but you have a blip on your liver and we need to do something to to sort out what it is. And then they write a report saying there is a 7 centimeter large tumor in the liver and which is semantically correct. But patient went back to her GP and was informed that she had the seven centimeter large liver tumor and then she was referred to to come. The hospital for further diagnosis seated in that any information to that came for a bapsy. And it looks like this so shortly after this she was sent home with a report saying the lesion has a typical appearance of a giant Hemangioma. And and from the time that she had the first exam until she was sent home with that diagnosis, it took two months. And and, uh, this is a sort of waiting time that we have to deal with in most most settings. And so for two months she thought she was dying. And I saw it again six months after this, and she was still having counseling because of trauma, so we shouldn't underestimate the impact we have on patients when when we can't give a certain diagnosis. Looks like that in the late fence, so summing up a little bit, the advantages, cost, benefit etc etc. When it comes to characterization. Contrast enhanced ultrasound is equal to MRI at 1/3 of the cost. When it comes to detection, it's equal to CT and half the costs in the Scandinavian setting at least. Ultrasound is also with contrast, extremely good at detecting perfusion or ruling out perfusion somewhere. And we can give contrasts in in catheters, in cavities etc. Show couple of examples in a minute. So now you decide that yes, OK, we'll start with artists with contrast and you go to a lecture and someone will tell you this is how to do it and you should do as the contrast guys tell you to do it because that is the right way. But if you basically just shake the bottle anyway, you want to fill the syringe, put the disc curb on your machines in a straight line, press the contrast button, adjust the gain so there's a slight background noise just to know that. Do that and then inject the contrast and scan as usual using the new criteria that you've learned then then you're fine. I'm just going to show you a couple of images here. This is a patient referred for. This lesion query. Can we see it on ultrasound for a microwave ablation? You have two images here. The one on the left. I've done everything according to the book, meticulously following the instructions on how to do it. The one on the right I've. Willingly. Made every mistake you can make. I have if it says shake it with your right hand. I've shaking the bottle with my left hand that everything that I shouldn't do and I think we all agree that the left image is slightly better than the right one. But when this was put, the same question was put to the same group of people that counted lesions before. We came up with this. So if if we sum a Group One and three up, so 80% thought the images were either equal or the one where I did everything right was slightly better. Some actually thought the other one was better, but the majority decided that the left one was better or they were the same. But if we put the question like this both images diagnostic, then yes, they are both diagnostic. Even when I made every mistake I could willingly. They they are images is still diagnostic so. Reiterating which we should always strive for the best in exam quality that we can have. So you should always do as the contrast guys tell you to do 'cause you get a better image if you do, but if you forget one step, if you make small mistakes somewhere, it's not a disaster. It's very robust system. You will get an excellent contrast image anyway, so don't be afraid of that. When it comes to characterization. We have a known focal lesion either by ultrasound, MRI, pets etc etc and we follow it overtime, so this is the short version is always very good to have a short word version as fullback, hyperechoic lesion scenario number one, enhancing a little bit in in. The periphery in the arterial face little bit more important Venus face and hyperechoic in the late phase scenario number two same hyperechoic lesion. Yeah, enhancing a little bit in the arterial face more uniformly. Or less I see code in in the Venus face, but hypoechoic in the mid face and this is this is the watershed. This is what to remember. If something is ISO or hyperechoic in the late phase more than 90 seconds, two minutes. It's very likely benign. Whatever it is, if it's hyperechoic it's very likely malignant. First one is a Hemangioma. The second one is metastasis. When it comes to detection, we're looking for the unknowns. Slightly different because we we need to to be able to scan through the liver and the obvious comment is we can't scan through delivering the arterial phase, which is fine, but we know that tumors that are the ones that we're really looking for. They will be hyperechoic in the late phase with a washout, so we can give contrast. Wait until we're in the late phase. And then we have several minutes to scan through the liver to detect something that's hypoechoic, and then you can re inject in that area to characterize the lesion. It's not a problem. This is typical situation where you have lesion enhancing in the arterial face. But the clincher is this is a washout in the late phase which means with very high degree of certainty that this is a malignant and this is where ultrasound comes into its own. Because these these breast cancer metastases are not seen on CT or MRI there three to four millimeters large and and we can use the spatial resolution that is really the strength of ultrasound. Now we have perfusion or ultrasound machines are very sensitive to the presence of contrast bubbles there so sensitive that we can say that if you have a contrast enhancement, we have perfusion, but if there's no contrast down sment, there is no profusion. So it works both ways. Again, it's a watershed that both both weights. A couple of examples here where where you have kidney with fractures in the kidney, the hematoma around the kidney here is obviously not enhancing because there are no blood vessels in the hematoma. Another patient young girl where we don't want to necessarily use CT and she has a temperature more than three days after being put on antibiotics for palina frites. So right kidney looks normal. Left kidney. We have a demetis area here and with with contrast it looks the same as it would have done on the CT where you had a hyper perfused area there. It's actually another one down here. Hyperfuse that hyper confused there saying same with the linear trust user with better spatial resolution, but we can say there's there's no. Hydronephrosis and there's no Abscess formation. And other patients where where query goldstones you have a little fluid collection upper abdominal pain. This fluid collection adjacent to the stomach actually juts into the lumen there, which is really fishy. So we gave contrast and even though it's basically anechoic, you still have an arterial phase enhancement here, and this is sort of situation that you might have. For example with lymphoma glands of Melanoma metastases that are there so. Hyperechoic that they're almost anechoic and they might look cystic, but if you give contrast because they have blood vessels, they will, they will light up like this. This is a small gist tumor. Another similar situation query goldstones query Cholecystitis and fair enough tests. Toned down there you have narrowing of the gallbladder. Here you have stones and what looks like sludge between those stones. But the sludge actually juts down there in a way that doesn't really look normal. So if we give contrast you have the same area. Here you can see that it's actually enhancing. And if it's enhancing, it has blood vessels, and if it has blood vessels, it's definitely not sludge. So if this is the situation then, then this must be involved in a tumor and you can actually see here in the late phase that we even have a washout. Another situation where where patient with NHCC. And it's large and patient was put on chemo when he came back for an assessment. The report from the CT here says that that this is so. This is now necrotic and the residual tumor is that, can you Blake that so we brought the patient up for an assessment for that and what you see is the residual tumor is down there enhancing in the arterial face. But you also see that was what was reported on the CT as necrotic. Even though this is a really difficult. Patient to scan large and with a cirrhotic. Still toxic liver. You can get the contrast enhancement up here so we can say that there's no need to have late this, because this is still viable tumor. That's still done. Vessels in there. Uh, and finally another example. You have an Abscess here in the service muscle patient was a. Weighing between 100 and 4000 and 50 kilos so we didn't think this was going to be the possible drain, but on on the B mode image with special transducers going deep you can see this area down here and it looks a bit strange. So with contrast again, if it's an Abscess there are no blood vessels, no contrast enhancement. So here you have the Abscess in the middle and we can. We can aim for that which we did put a catheter in and pus came out. And just two two final things. This is the first one where you have a patient with with lower, lower abdominal pain. Slightly dicey looking balls down here and this is called an Abscess. It is an Abscess in in the wall of the urinary bladder. With contrast, it looks like this, so it's a small Abscess here. Not worth putting a drainage in, but we decided to stick a finding Lynn to get a sample out. And and at the same time as we did that, we injected contrast and then it looks like this. You have leakage into the urinary bladder. There and. Wait for it. Then you have a leakage into the bow in the other direction. So this is actually a fistulation from bow to a little Abscess in the urinary bladder wall and into the early bladder, and from this diagnosis it was when when nervous was taken further, it's obvious that the patient has Crohn's disease. And the second one I want to show you is this. This is a patient before giving contrast, and five minutes later with after having given contrast. I'm not entirely sure. I'm sure the contrast guys knows know what this is, but it doesn't mean anything. It no elevated liver enzymes and within 24 hours the level will look completely normal again. It's not very common, but if you scan if you do this on a regular basis you will see it. In time to time, don't panic. It's nothing to worry about. So. And just finishing off, we're now two, two 2021. None of us would dream of doing a CT or an MRI without contrast, so why should we do control ultrasound without contrast when we know that it improves diagnosis in many cases? And in conclusion. Contrast enhanced ultrasound is not rocket science. It's different from a B mode image. Uh, and but it's easy to learn and it saves time and money, and it saves a lot of worry for your patients, so go for it. I think it's it's quite an easy thing to start out with. Dear Chairman, professor possible. Hello everyone, I'm Kenya from Peking University Cancer Hospital. Thank you very much for your invitation to easier conference. My topic today is contrast enhanced ultrasound in liver imaging. Y CUS should be the norm. This is the latest version of Chinese guideline for diagnosis and treatment of primary liver cancer, which was a consensus statement of many multi discipline experts in China, including the ultrasound expert, Professor Leung, Ping, etc. But the noodles of less than two and greater than two centimeters CUS reported as Firstline mortality after detection by B model ultrasound in Chinese primary liver cancer guideline. In China, the number of hospitals using CUS is increasing, especially for the last five years. The number reached 2143 hospitals in 2020. CUS can be applied into many clinical aspects. And liver application is the most fundamental one in almost each hospital in China. In China, Department of Ultrasom initial DC US applications in the hospital. Nowadays, due to the widespread of minimally invasive treatment, many clinical departments also embrace CUS. Take liver as an example. Department of Surgery, intervention, cancer and even internal medicine include CUS as a clinical rooting for diagnosis and treatment. CUS liver applications mainly involve diagnosis and intervention. First, let's look at the diagnosis. They use CUS for characterization. PS1 was a patient with FCC, two DUS show right lobe, hypoechoic lesion, no HPV history, AFP level larger than 400. See you as show segment six arterial face marked hyper enhancement. Late and mild washout. Case two was a patient with Hammer Joma. 2D US show right back lobe hypercoagulation 5 centimeter. CUS both AP and PvP showed progressive centripetal contrast feeling and no contrast feeling inside the nation. Case Three was a patient with my test tests. Two DUS show segment, eight hypoechoic solid lesion, 3 centimeter arterial face rim hyper enhancement, some hypo enhancement area inside. Early and marked washout with hypo enhancement. There are many studies on focal liver lesion characterization showing so now we'll see US has good sensitivity and specificity with similar efficacy compared to SCT and CMI. Oh, I see. Guidelines showed the sensitivity of CUS ranged from 82% to 95% for characterization of focal liver lesions and detection of liver metastases. No evidence of a difference in performance among imaging modalities. CUS was slightly more effective than city and MRI and less costly. In terms of diagnosis, the ability to find deletion. LSAT guidelines report CUS to be similar to CCT&C MRI for diagnosis of liver my test tests. This started this study. Tell us, see you as reliably offers typical size of small liver metastases. Differentiate effectively with small FCC's. CUS can help to improve the diagnostic confidence of small liver metastases. Our center is also conducting a prospective study on liver metastases using sonar view microbubbles and Simmons as. 3000 scanner we compared CP S&CHI technicals under metastasis detection in this work. Patients with color rectal liver metastases treated with two to eight circles of chemotherapy. Underwent conventional 2D US gas and randomly divided into two groups. CHI group and CPS group. Then randomize the sequence. Patients underwent surgical resection. We took the surgical pathology and interruptive ultrasound as good standard to evaluate DCI and CPS diagnose efficacy. This is our initial results. Showing that KTVI technical is open is able to detect more lesions. Compared with CPS. Especially for those small lesions under 1 centimeter. This is an example. A 75 year old male liver metastases were found three months after surgery of rectal cancer. Chemotherapy of silox had been performed for three cycles. Conventional ultrasound we can find three nations only. We switched to see hi ultrasound. We detected Six Nations. There were from #1 to #5 lesions. #2 and #3 near liver hepatic vein did not show with CPS, but we can see in CHI. This was the number six leisure from this video we can see alition. Showed clearly in CI. See, I try. And not clearly in CP SCICPS. In intra operative ultrasound confirmed metastasis and underwent radiofrequency ablation treatment. Next we look at the value of CUS in biopsy. This is an early retrospective study from our center showing that the USB for biopsy improves diagnostic accuracy. Particularly for those lesions smaller than two centimeter. This is our further prospective study. The multicenter study of cutaneous focal liver lesion biopsy guided by CUS. Which has been accepted as a poster presentation by ECR last year. Will complete enrollment of 2088 patients from 9 centers. The diagnostic accuracy, negative predictive value, and sensitivity are significant higher in CUS guided biopsy group compared with US guided biopsy group people value less than 0.05. CUS plays an important role in guiding liver cancer treatment. Firstly, we can use CUS to determine the lesion sites before treatment. This patient had a 3.4 centimeter liver lesion. Showed unconventional to EU S. The boundary is not clear. Undersea US imaging. The lesion showed us sets of two. Centimeter in atere face. After surgical resection, it proved to be HTC. We shout and capsulation. The specimen was obtained from the contrast enhanced region showing on CUS images. Which the boundary was not clear presented onto the US image. The results showed that hepatoma cells and how heptyl sites grow at natively without clear boundary and area can detect the abnormal blood vessels. It indicates that the hyper enhancement of Hyper Vascular area near the tumor is associated with tumor infiltration. Our retrospective study also suggested that among recurrent SCC patients, there were 59% patients showed increased station size on CUS compared with two DUS. 10% and chanted. 23%. Decreased 8% Princess on CUS but not sure on R2D US. The RFA treatment planning was compared between based on the site from C US and from 2D US. The RFA treatment results showed that successful rate of CUS Group was significant higher than that of 2D U.S. group. And the local progression rate of CUS growth was significantly lower than that of 2D U.S. group. During the treatment, CUS helps to guide location and determine bleeding etc. Ah, 14-8 year old male. Reset resection of left lobe because of at CC. In the follow up exam, MRI found two recurrent HCC lesions. The apple three images 2D US can show the relatively large lesion in the segment 7. 28 near the diaphragm. The lower three imaging, however, 2D US can barely locate smaller lesion in segment 8. So we applied both volume navigation. And see you as technicals. It allows the guidance from MRI images showing the location of the small nations. Then in jackets Onoville when hyper enhancement in a terror face appear, we can localize and characterize deletion. Under the guidance of real time CUS, deletion was depicted in anterior face. Then we inserted the needle and performed ablation treatment. We saw the help of CUS. We cannot localize and treat these lesions at all. Another case. 17-5 years old. Male received Ivy for liver metastasis of colon cancer. 5 minutes after the treatment accumulated effusion was found in the front lever which was detected bleeding. After intravenous injection of sonar view, we can see obviously bleeding from the road where the ablation needle was inserted. With the help of Microbubble, the location and speed of bleeding can be observed clearly. After detecting the bleeding site, we inserted ablation needle along the bleeding road and applied multiple ablation for small areas to stop the bleeding. After treatment, see US can be applied for evaluation of treatment response for short and long term. This example is a typical HCC. The diagnosis was definite before ablation. CUS showed. CUS showed hyper enhancement in arterial face late and mild washed out the nation. Sites was around 2 centimeters. We used umbrella shaped Ivy electrode and a sophistical treatment range of four centimeter was set. Stab Lish and procedure was normal. And larged. High priority area was seen on 2D US. Immediately after Ivy treatment CUS was performed. We found the updated area was different from expected. The ability nation was not globular, which means tumor viable tissue still exist. So another ablation procedure was conducted and CUS was performed immediately after the application, the images showed up late edition was closed to be globular, meaning the ablation was successful. From this example, we can see the immediate evaluation after treatment can help us assist. Did treatment and give. Campo mentions abolition when necessary. Summary CUS is real time easy to observe and operate. It can clearly show microvascular perfusion of targets. It plays an important role in liver lesion diagnosis and treatment. Thank you very much for your attention. Thank you very much. Professor Nielsen and Professor Kwan for the excellent lectures that we both heard. Now two different lectures, one on the basics of how you set up and run a an ultrasound contrast service. So very important to get this right and a second more detailed lecture and bringing out the the superb use of contrast in elucidating problems and getting to the end of the the question that's been asked. So in this discussion, now we're going to just run through some questions and get some feel for the background to to some of the. Images and the. The discussion that we've had previously. I'm going to start with Professor Jan. First of all, I'm going to ask you what is the situation in China with the use of contrast in the ultrasound department, because I know the setup before ultrasound in in China is very different from what we in Europe in particular used to Professor Young. Thanks, we are question in China. There is an increasing number of ultrasound departments performing. See use in their routing in the hospitals and now the number is more than 2100. In these hospitals, CUS is a very important component in the ultrasound examinations, particularly for ultrasound interventional procedures, including before, during and after treatment. So CUS has become a fundamental imaging technique for ultrasound doctors in China. In Europe, most of the outer circle exams are performed by sonographers and diagnosed by ologist in the radiology department, while the ultrasound department is stand alone and independent. In China, ultrasound doctors prescribed exams for patients with CUS indications based on conventional ultrasound exam results. So this will save patients time and we believe this is a quite efficient system. Thanks chairman. OK, that's very interesting in China. I believe the the doctors trained only in ultrasound, so they're not in radiology. They're not other physicians, and they do all aspects of ultrasound. Is this correct, right? Yeah, so this is different from what we are used to in Europe. You mentioned sonographers just now. In Europe, sonographers are really a phenomenon restricted mainly to the United Kingdom, and there are other. Areas in Europe. In Israel, for instance, that use sonographers and the same in the United States of America and Canada and Australia, where sonographers are used. But in Europe the situation is slightly different in that it's not just radiologists that use ultrasound, but many other physician groups as well. Doctor Nielsen, I'll bring you in there. What's the situation like in Sweden with regards to ultrasound and contrast enhanced ultrasound? It's a I would like to be able to say that it's a pillar of radiology and for quality it is a pillar of radiology. But in in when it comes to the use, it's sadly underutilized. And and and. I think to, to a large extent it's not because we can't get the clinicians to refer patients to us because I think it's it's the case in in many European countries that whatever the referring physician says he wants as an exam, we have the right to convert it. If someone sends something for an MRI to assess an incidental focal liver lesion. You have a right to just change it to a contrast enhanced ultrasound. Uh, and I think the problem is more with our our radiology colleagues that it's a lot of people will say, right? Well, we'll just do an MRI to be on the safe side, and I think it's we've had a problem getting across to a lot of our both radiology colleagues. Another ultrasound using doctors and the referring physicians in that. They they are not quite aware of of the the potential, and they're not quite aware of the literature we're supposed to be. 2021 were supposed to be evidence based and and the evidence that ultrasound in some instances or a lot of instances are equal to or better than CT and MRI is not quite there I'm afraid. Yeah, I totally agree with you. As a radiologist myself though, I don't practice outside much out ultrasound now, but it's very easy for the radiologists to get to take the easier route because they are busy with something else and ask for a CT or MRI. Yes, and the situation in Europe is that where there are non radiologists practitioners using ultrasound for instance the hepatologists and I'm talking particularly about Germany and Italy. They use a lot of contrast enhanced ultrasound because. They don't have that ready access to the MRNCT that radiologists like yourself and myself have, and this is where the model of actually having ultrasound departments that are only for ultrasound, like in China and I may add in Russia as well, follows the same sort of model as in China, and correct me if I'm not wrong. Professor Young, but you, under pressure to provide a diagnosis with whatever is under your your are in you within your department. Uh, about uh, we just finished a prospective, multicenter randomized study to compare CUS and conventional US in guiding proteinous biopsy. Or focal liver lesions. We random randomly divided patients into two groups. The diagnostic accuracy of CUS guided group is significantly higher than that of conventional US guided growth. For the subgroup analysis, we also found that CUS guided biopsy is practically useful for those small lesions smaller than 3 centimeter, especially smaller than two centimeters when nations are small CUS help us better locate and visualize cancerous parts for HCC within the hyperplastic nodules and better differentiate necrotic parts in the cancer tissue to improve biopsy diagnostic accuracy. Believe this will be useful and practical in the future clinical norm. I can't this. This demonstrates to us that in the ultrasound department in China, where they're not going straight to CT or MRI, they're using ultrasound contrast to its complete ability to make the diagnosis, which is which is really very very useful. And is how are you going to influence your colleagues to send you more patients to actually do the ultrasound? I mean not talking just about liver. I know it's only a licensed in in liver technically, but we also have colleagues in neurology who we've seen managed to convince that ultrasound contrast of those cystic partially Bosniak cystic lesions is really useful. How do, UM, Flint, your colleagues to get them to send you more patience? Well, I'm I'm using, uh, just as as we're speaking a combination of sticking carrot because I tried only carrot and then I've spent two years in in the place where I'm working now and it hasn't completely worked. The situation has improved, so now we've we've come up with a PM that says, right? We have in these particular instances you have. To give contrast and and and explaining why so with with reference to to the existing literature and the reasoning. Why do you have to to give contrast? For example, if if we do very basic ultrasound query gallstones find liver lesion, we know that if we put event flown in give contrast, characterize it in the same instance. We send the patient home with with report that says gallstones are no gallstones. Hemangioma in the liver and they won't be able to. They won't return. Everyone can see the benefit of that. The patients are not coming back through repeated ultrasound. They're not coming back for an MRI. They don't have to wait three months worrying that they have a liver tumor. So so come get getting my colleagues to sort of suggest ultrasound and use ultrasound contrast and I believe that when we show the results then then the clinicians will start referring straight to ultrasound as well. That's a very important point you brought up about the incidental lesion because when you get referrals from the primary care physician and I'm sure this is also the same in China and you find an incidental liver lesion. Almost 90 to 95% and we're talking about a patient who's got no background. Cancer is not coming from a cancer clinic this coming from the community with an incidental lesion 90 to 95% of the time. This is a benign lesion, so why should you subject that patient when you have the ability to tell the patient? Yes, it's benign. The patient is watching you doing this scanning, and if you find a liver lesion they're watching your face, your face will suddenly change because you've found. Something that is not expected. The patient understands that there's something going on, and if you can reassure the patient within 10 minutes of an outside examination that you found the most common focal liver lesion, which is the Hemangioma. Yes, yes, that's it. Yeah, it it stands to reason that if if you choose to become a radiologist, the psychological side of things is not your main interest. So, but I think we seriously underestimate the trauma. Of going to come to your GP and in getting the report that yes, you have a gallstone. But you also have a blip in your liver and we need to do another exam to be absolutely sure that it's nothing because the even even as you say, in 99% of these cases it's it's been 9. But you tell the patient those odds and they come to the car park and the odds have shifted in their heads and then they spend three months waiting for for another exam. Feeling absolutely sure that they have something in the liver that shouldn't be there, yeah, but of course it's the mindset for the radiologist in Europe that ultrasound is not putting any needles in there. Yes, you don't want to have. This becomes a big problem. It's a hurdle, but I've been to China and I've I've been to to the Sun Yat Sen University, first affiliated hospital and I've observed the standards of ultrasound and the the organization of the department. In China, where everything is done so well that if a patient needs an ultrasound contrast examination, everything is set up there for it to be seamless and working very well considering also the volume of patients that Professor Young sees. But you also used contrast. Enhanced ultrasound professor Jan after liver interventional procedures. How does this help you? Can you reiterate and tell us how how you use this in interventional procedures? During and after liver interventional procedures, the unique value is real time. I think it can guide middle process precisely for treatment, which is difficult for contrast. Enhanced CT or MRI. Gold standard to treatment evaluation. Focal liver cancer is still contrast enhanced CT or MRI. CUS is more advantage Lee in the immediate evaluation after treatment. This is practically useful for those large tumors that require multiple needle insertions. We have to evaluate if the treatment is complete, so we need multiple contrast imaging. Give us real time and immediate response and this is achieved by CUS technical which is mostly by sonar view in China. It, uh, if we find residual tumor. By CUS, immediate treatment can be performed and to improve success rate for local treatment, thanks. That's very good. I mean what you're showing here is a more or less innovative point of care. Can I'll contrast help you? And this is thinking outside the box all the time. There are situations that you think. What else can help me here and contrast inevitably Canon? There are many situations where we use contrast just to get that final answer to help us. Now I'm going to end up that it's discussion with Anders here and talk really about. People who are just starting off on the the journey of contrast that you and I and many others have been on for 20 years, so it doesn't look like 20 years. In your case, more like. But anyway, how? What is this learning curve? How difficult is it to get up and start? Because we're experienced practitioners. Now we can't remember learning how to do it, yeah? Well, I'm so I'd like to start by quoting Professor Torben Andersen. He was one of the Swedish ultrasound pioneers in in Erbil which is actually my hometown and when I had had my first locum as a 25 year old medical student in radiology, he said one day you have to just get into the mind frame and say to yourself right. I know this type of exam and then I start reporting it. You, unless you actually decide that yes, I know this, I have to start doing it then then you'll never get any further so you have to start doing it. And actually I think the learning curve is is very short. You you can't expect to know everything the first few days that you do do. Contrast enhanced ultrasound, but you can start by saying fine. If I find a focal liver lesion, I'll give contrast and try to characterize it. If it's a typical Hemangioma, then write that. If it's not a typical Hemangioma then you going out someone for help 'cause you can still record the image overtime and get somewhat same as with the MRI. Go and ask him more experienced colleague and overtime you develop more knowledge about OK when it looks like that, it's that. When it looks like that, it's that, but. I mean we had we have sonographers in Sweden as well and and we're getting more more and more and we have affiliated with the university as a smaller hospital on the South Coast and they have very few radiologists that they have. A brilliant sonographer who takes care of all the ultrasounds. In in the autumn she came to to to learn to spend. She spent three days with me here doing about 10:10 Cos contrast studies per day and then we had the same number of patients for two days on her own machine, down, down, in, on the South Coast, and for the first first couple of months she would use the chat. Function in the pack system as a right and as I did this. What you think of that? And and now she rarely bothers me anymore. She'll just write the reports so he really just if it is to learn how to do the ultrasound and you did that before, exciting. The contrast is very easy. Yes, yes, and I think your problem is is that to get people to use it because. Uhm, an ultrasound without contrast is still unacceptable. Exam in in the settings where where if you don't have contrast, you can still look for focal liver lesions. No one in their right mind would dream about doing a CT without contrast with when the query is focal liver lesions, 'cause that's absolutely useless, but native ultrasound isn't absolutely useless, just that contrast is so much better. Yeah, OK, thank you very much there, and that's very informative. And I'm very pleased to hear that. You're also now expanding and getting some sonographers into Sweden. Yeah, and just to finally just touch bases with Prof Jan. I don't understand that you in Beijing and your hospital that that you don't have sonographers, but I am. I do understand that the Western China Hospital their program includes sonographers as well who are doing contrast enhanced ultrasound. Have you heard of this? Yes yes yeah yeah. So it's it's something that you know. Using contrast and getting everyone who's using the ultrasound as a tool, whether they're physicians in hepatology, radiologists just, ultrasound based physicians, and our colleagues in sonographers and vascular technicians, they should all be encouraged to use this to add it to their there. AMA martinov of techniques. So I'm going to thank both of you very much for your lectures earlier on and it's been great fun having a discussion and bringing out some very important points, learning about practice in different countries across the world, but let's hope that in the next time when we all meet its in person together and we can enjoy each others company. So I thank you very much. Thank you very much. Professor, thank you, Anders. Thank you.

HOW? "02 Early Microbubble Contrast Trials: Early Micrbbåbbie Contrast Triåts: Contrast Enhanced Ultrasound: Microbubble Contrast Enhanced Ultrasound: 01 2021 Why? Microbubble Contrast Agents: woo 03 THE SHORT VERSION 2D US US CEUS-Avp CEOS-A?p CEOJS-A?p CEIJS-Avp CEUS-GB CEUS-pvp Results (DO AS THE CONTRAST GUYS TELLS ULTRASOUND CONTRAST 2. Determine the bleeding site 2. Determine the bleeding site (video) I. Fusion imaging-guided ablation I. Immediate CEIJS evaluation, change in management I repeatir 1. Fusion imaging-guide d ablation 1. Fusion imaging-guided ablation I. Immediate CEUS evaluation, change in management I repeatir I. Immediate CEUJS evaluation, change in management I repeatir ECR 2021 MIO 0 To confirm infiltration boundary of liver cancer before ablation Technical Route us Portal Vein Patency Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Ed Guidelines for Diagnosis and Treatment Of Primary Liver Cancer in China (2017 Ed Conventional ultrasound: 3 lesions detected Imaging Techniques Peripheral A/ascuTar Ärterial Disease Dept. Of Surgery Liver Transplantation Arterial Patency Peripheral Vascular Arterial Disease Focal Liver Lesions CHI ultrasound: 6 lesions detected • INN Satellite Symposium hosted by Bracco and Siemens Healthineers Safety WHY NOT? WHY N0T? In 2020. 4C1-s Detection of lesions compared between various methods CEUS before RFA: 290 Recurrent HCC (RHCC) lesions schedule &your Wei Wu' 2021!!!! neo Tao HOW MANY LESIONS DO YOU SEE ? ARE THEY BOTH DIAGNOSTIC? WHICH ONE IS THE BEST? CHARACTERISATION WHY CEUS IMPORTANT!!!!!! CONCLUSION DETECTION WHY? History PERFUSION PHASES el-s A Multicenter Randomized Controlled Study of CEUS- and US-guided Percutaneous Biopsy o A Multicenter Randomized Controlled Study of CEUS- and US-guided Percutaneous Biopsy o Iver Contrast-enhanced ultrasound features of Iver Lesions Iver Leslons ablation, success during follow-up evaluation Iver eslons Metastnalysis Meta-analysis Metastasis N Of studies YOU....BUT...) N Of lesions with eslons using CEuS in China using CEUS in China 07 02 Min-Hua Chen' NICE guidelines report CEUS to be similar to CECT and CEMRI for the diagnosis Of NICE guidelines report CEIJS to be similar to CECT and CEMRI for the diagnosis Of Role of CEUS in Radiology Microbubble-enhanced US in SonoVue (sulphur hexafluoride microbubbles) — contrast agent for CEUS AS THE METHOD OF NHS histologically proven small (S20 mm) liver Shan-Shan Specsificity Spensitivity SonoVue 'Doppler Rescue' for Liver Lesions Liver Conventional Ultrasound Dept.ent of Ultrasound CPS CRLM that had been treated CHI No. 6 M JER The Role of Contrast-Enhanced Body Imaging: moe?' Body Imaging: me?' Body Imaging: Body Imnaging: Body Irnaging: me?' Body Imaging me?' Body Imaging Body Imaging Foe?' Body Imaging moe?' Body Imaging: Foe?' No. 1 H ospita\ No. 2, 3 No. 2, 3 Siemens Health Siemens Healthineers presents Biopsy • Biopsy Kun Yan' liver metastases in 4 studies analyzed Enrolled 2088 patients from 9 centers in China National Institute for • Blood pool agent contrast-enhanced ultrasound imaging of the liver Comparison of Contrast Pulse Sequence and Contrast High-Resolution Diagnosis ntervention 2. bleeding site Cancer (range) (range) The size change of RHCC for 2-8 cycles of chemotherapy and has undergone MRI HCC Repeating ablation High Mechanical Index (Ml) Technique metastases • 1. Shake the bottle and fill the syringe Zhi•Hui Fan' Gastroenter;logy Zhi•Hui 12 RFA treatment results Much 5' , Health and Clinical Excellence Visible lesions 226 320 Gastroen Expensive — not compared to e.g. MRI contrast Issued August 2012 CHOICE ontrast-enhanced ultrasound in liver imaging — Characterisation Sonography of Focal Liver Lesions King'S college - Sensitivities 83% across modalities "Role of CEUS in RadiologV' "Role of CEUS in RadiologV/' "Role of CEUS in Radiology/' NO Wei Yang' parallel group, randomized design ox wei 1-2 ml intravenously Treatment Alt. 1 Alt. 2 Friedrich-Rust M 45 7231 93% measured by CEIJS before RFA measured by CEUJS before RFA measured by CEOS before RFA • Characterisation: CEUS = MRI; CEUS = MRI Cost x 3 Cost x 2 196CYs, agitated saline used in echocardiography • l. Abest • Patient Treatment . l.Yes • Patient #2 . l. Yes • Expensive CEUS is not rocket science The Hemangioma group (Boomerang diagnosis) 40% The small lesion in the middle of the • Known focal lesion (by ultrasound, CT, MRI, PET etc.) • Looking for the unknown • This is NOT a contrast enhancement of the B-mode image 00 c CO c Imaging Modes of CEUS for the Diagnosis of Colorectal Liver Metastases — Diagnostic NICE diagnostics guidance 5 • Our ultrasound machines are very sensitive to the presence of contrast CEUS = CEUS-Ap 5% We would not dream of doing CT or MRI without WE SHOULD ALWAYS STRIVE FOR THE Destructive Mcxie: Adverse events 29 investotons Adverse events 29 investotöns Adverse events 29 investogatönsk Adverse eve•nts 29 investotöns Destructive Mode: Destructive Modie: Invisible lesions (missed Biopsy • Biopsy Diagnosis s 1.1 • None 50/6 O d • — NHS o d - Conclusion: ". ...contrast enhanced ultrasound alone may be adequate to rule out liver - Conclusion: "....contrast enhanced ultrasound alone may be adequate to rule out liver Before Percutaneous Biopsy perform routine ultrasound Perform routine ultrasound Perform routine ntervention OdB/DR7 OdB/OR7 hy CEUS should be the norm • Detection ntervention oo Yi Dong. Zhang. Feng Mao, Bei-Jian Huang Qin Si & Wen-Ping Yi Dong Xiao-Long Zhang. Feng Mao, Bei-Jian Huang Qin Si & Wen-Ping Yi Dong Zhang. Feng Mao, Bei-Jian Huang Qin Si & Wen-Ping Two arms: US- and CEUS-guided biopsy Ling Past: Only Dept. Of Ultrasound, mainly for diagnosis and characterization The size Of red bloodcells The size Of red Development was slow because Of technical limitations Development slow because Of technical limitations (Compared with US) nausea. sense warmth Microbubble Microbubbles • Dangerous — very low toxicity (if any), allergic reactions rare • 2. Put the DGC-curve in a straight line 185 142 nausea. sense 5th March 2021 (Before, during CPS • Remember; the image updates with around 20 fps = a realtime exam Remember; the image updates with around 20 fps = a realtime exam cps Benign or • Characterisation right liver lobe was 0.8mm • Optimizir" of in doartment • Optimizir" of in doa•tment • Optimizing of in doa•tment • Optimiing of in doa•tment • Optimizing of in • Optimizing of in doartment bubbles. Ji-You Li2 Contrast-enhanced ultrasound with SonoVue (sulphur exa ina Characterisation Treatment Niu Y metastases in people with known priman/ malignancies. " metastases in people with known primary malignancies. " 45 185 10 878 Wang diagnostis) diagnosis) Diagnostis) RADIOLOGY' BEST EXAM QUALITY....SO.... BEST EXAM QUALITY....SO Ditz i ness Din i ness Din i rms Din i rw•ss • Dangerous rate (1 month) progression time HEALTH TECHNOLOGY ASSESSMENT A Prospective Single-center Study An a b s tract An Last 20 years has witnessed an explosion in development driven • Treatment of CEUS in 2013 20213 contrast. ... (91-95) Ande•s CEUS considered a first line modality RFA treatment hexafluoride microbubbles) compared with contrast-enhanced CT • Detection Rtesvection tore I 2221 Transient I maging Transient Immediate CEUS evaluation Immediate CEIJS evaluation and after) presented as a Prof. Kun Yan pt al. Prof. Kun Yan et al. Rafaelsen et al. compared SonoVue CEUS to CE-MDCT for the diagnosis of (mean, Switched between CHI and CPS modes by the discovery Of patterns Of acoustic behaviour Of the Dtetvection (OR....WHY ISN'T (OR. ...WHY ISN'T • ultrasound im"ing: why be • im"ng: why be • im"ing: why be • im"ging: why be • imaging: why be • ultrasound im"ng: why be • ultrasound imaging: why be • Ever im"ing: why be • Contrnt-enh&ced im"ing: why be rate , during • Difficult — basically ordinary scanning but with new criteria Total number of lesions of Grou 'Yo ( atient no. 'Yo atient no. atient no. P value Andes • Detection • 2.Bbest • 2. Yes but... • Patient #2 • 2. B best ntervention Different from a B-mode image 64-year-old male with cirrhosis (autoimmune) 5% 0% Km Random grouping DO AS THE CONTRAST GUYS TELL YOU ! CEUS = CT CEUS = CT; Wd • 3. Press the "contrast" button (Before, Guang 10 7231 2981 20213 scientific exhibit and contrast-enhanced MRI for characterization Of focal liver SIEMENS Kun TO cite this article Yi Dong Xiao•Long Zhang Feng Mao. Bei•lian Huang Qin Si Wen• TO cite this article Yi Dong Xiao•Long Zhang Feng Mao. Bei•Jian Huang Qin Si Wen• TO cite this article: Yi Dong Xiao•Long Zhang Feng Mao. Bei•Jian Huang Qin Si Wen• TO cite this article Yi Dong Xiao•Long Zhang Feng Mao. Bei•Jian Huang Qin Si Wen- • Follow over üime • Tumours will have a late phase wash-out • Follow over time Imagirw (Before, during Andes • Difficult 301 +59=360 (liver metastasis 347 lesions) • Detection: Guidelines for Diagnosis and Treatment of Primary microbubbles range in metastases Benign hemangioma Dept. events Dept. of Internal Medicine • This is a completely different way of creating an ultrasound ntervention Dept. of Intervention • Arterial phase; the echogenicity depends on vascularity (amount of vessels) 20213 Arterial phase; the echogenicity depends on vascularity (amount of vessels) (35l With SonoVue) (12l with SonoVue) (83-88) (79-84) (poster). C-09351 (poster). c-093S1 (poster). c.093S1 c.093S1 C-09351 c-093S1 Ping Wang (2016): Contrast-enhanced ultrasound features of histologically proven for the same slice Andes CEUS before liver biopsy improved the 0.9092-0.9413 lesions and detection of liver metastases: a systematic review and after detection by B-mode ultrasound 2011 Follow-up 21 2221 and Hem angioma Hem angiomna Liver Cancer in China (2017 Edition) Diagnostic Diagnostis • User dependent — everything is TABLE 4: Mangnant in TABLE 4: in TABLE 4: Malignant in Last few years a consolidation in knowledge and practice < 0.2 small mm) liver metastases. Scandinavian Journal Of Gastroenteroloo•. DOI: small mm) liver metastases. Scandinavian Journal Of Gastroenterology. DOI: small ('20 mm) liver metastases. Scandinavian Journal Of Gastroenterology. DOI: Department of Ultrasound, and after) •2 - Sensitivity 85.7% for both modalities, specificity 97.6% vs. 95.6%, respectively J-7 VIENNA J-7 Sensitivity 85.7% for both modalities, specificity 97.6% vs. 95.6%, respectively Gas with a stabilising shell Shanshan Yin, Kun Yan', Chao Zhang, Binbin Jiang • Co contrast enhancement = no perfusion • No contrast enhancement = no perfusion CHI scan, store images CHI scan, store images CPS scan, store images my ESR.?RC my ESR.2RG Dept. Medicine Low Ml technique cost-effectiveness analysis • User dependent • 4. Adjust gain so that there is a slight background diagnostic accuracy Of the procedure by Accuracy CEUS-GB image. Detection of small lesions (