Malignant Focal Liver Lesions - HD

Introduction

Thank you very much for inviting me to come to this course here in London. And I'm very happy to speak here.

Malignant Focal Liver Lesions

And first topic I'm gonna talk about is not the BE nine one, but the malignant ones, sorry, malignant focal liver lesions, mainly, of course, understood as metastasis.

Diagnostic Goals

So our diagnostic goals that we have with these malignancies is number one, it's detection number two characterization that you just heard from David's. So a differentiation from B nine lesions, of course. Number one, the type of tumor we can very often characterize and the vascular supply important for interventions. And then of course, follow up under chemotherapy or immune modulating therapy, ablation therapy, surgery, or spontaneous cause of disease.

Imaging Techniques and Contrast Agents

So of course, it's also important at that point that we have to look at the techniques that we are using to image contrast agents. So here are different ones. And you heard already in our, in the first talk that we have two major techniques. Number one is amplitude modulation imaging technique, a MI, that has the advantage of the penetrating very well and very deep into the liver. That is the advantage. The disadvantage is it has some kind of blooming. So the temporal resolution is the spatial resolution is not as good as in the technique that was used previously. That is the ation imaging technique. And that has very good and up to now the best. Nearly the best spatial resolution, tissue suppression is not as good as in amplitude modulation technique. And then we have new ones. The one that I'm showing lots of images of is these low mi harmonic imaging mode. We named that high rank, and I developed that in December, 2009. And that was thrilling. I showed you the very first loop of this technique. And then of course, we have B flow that is patented by ge. But I learned that also, of course, Toshiba has a similar technique, and I think both techniques can be used for using contrast. So the advantage of B flow and contrast is that it has the best in class tissue suppression, but of course, we get no information about stationary echoes. That is very important. So the use of this technique is very limited.

Benign Versus Malignant Tumors

Okay. Benign versus malignant tumors, you already heard that there'd be nine lesions. Show hyper iso enhancement overall contrast phases. So benign lesions are best detected on B mode, of course, number one, but also during the arterial phase because of the late phase ISO enhancing with the surrounding tissue. So you will not detect it in the late phase. You will detect it in the arterial phase or ingra in gray scale. So that is like FNH or hematoma. At the malignant lesions, they wash out, metastasis mostly during the late arterial phase or early portal venous phase.

Contrast Arrival Time in the Liver

So it is important also to look at the time that is being needed for contrast to arrive in the liver. So in healthy subjects, and we looked at that. The average time for arrival with contrast in the hepatic artery is about nine seconds, nine to 10 seconds. The time interval before the contrast is entering our the portal venous system is about three seconds. So we have three seconds time to image the complete arterial tree. That is not very much, but we can do that. Number two is after the contrast arrives in the important vein, it takes some time until you can see the first bubbles appearing in the HEPA veins. So that is roundabout to 21 seconds. So it is important to have these numbers in mind when we look at lesions and their contrast behavior.

Reasons for Differences in Tumor Enhancement

The next question is, of course, what is the reason why we see differences in tumor enhancement between benign malignant and among malignant lesions? Number one is, as you all know, probably we have tumor vessels that are leaky. And the leakiness of tumor vessels is important because as soon as fluid is being pressed out into the inter of tumor, then the pressure in the tumor is rising and due to the rise of interstitial pressure, then the number of vessels entering a tumor, especially in the center Of the tumor, is going down. So that is one of the reasons why chemotherapy does not reach all the Bible, but ischemic areas of the tumor. Number two, that causes, of course, tumor ischemia and necrosis. And we have that is also a characteristic thing about malignant tumors. We have a very high microvascular density. They can make up to 10% of the weight of a malignant tumor. Shunting is also very common, either within the tumor or even shunting that will cause changes in the surrounding tissue. And then we have a high density of tumor cells. That's also important when we look at tumors, and it's always a good idea to go to pathologist And have a look at the microscope. How do these tumors look like? How big are the tumor Cells in comparison to the hepatocytes? And you will find out that, for example, in the kin lymphomas, the tumor cells are much, much smaller than the hepatocytes, but much more densely packed. And this results in a washout by the late arterial or during the proven venous face. Of course, as we just heard by David, that we don't have these sinusoids in malignant tumors that are course correct, but also in hemos we have no sinus cells and they also do not wash out. So we have to look very carefully at the vascular of tumors.

Contrast Characteristics of Metastatic Liver Lesions

Contrast characteristics of metastatic liver lesions. Number one, the tumor related changes of the contrast kinetics. Number one, we have the arrival time, some tumors in some tumors, the contrast arrives very early before the arrival in the liver parenchyma. And then we have a change in the transit time. That means the time between the arrival of the contrast in the hepatic artery and portal vein at the time that is passing until you see the bubbles appearing in the liver veins. So this is mostly shortened in malignant tumors. The vessel architecture is maybe chaotic in may show a spoken wheels sign, a basket sign or regular branching. Sometimes you can see that in cdo, but mostly, of course, seals is much more superior to these common techniques that we use to image the macrovascular filter of the tumor, the flow direction. That may be interesting. And you already heard that cent peel or fu enhancement that is important and we will have a look at that later. The strength and duration of enhancement is of course, a characteristic feature. So we look if the tumor is hyper enhancing, iso hypo enhancing the enhancement distribution in the tumor is important. So does the tumor enhance homogeneously or do we see areas in the tumor that are more enhanced than others? Or in other words, are the ischemic or necrotic areas in the tumor. And then we have something that we name the tum enhancement. So when you look not at the tumor itself, but if you look at the effects that a tumor and the vascular situation of a tumor produces, then we will see shunting shunting, for example, in the periphery of a tumor. So it this is not tumor, but it's an effect caused by the tumor. We see posterior enhancement, we may see sharing. These are all effects that are being caused by the tumor itself.

Detection of Tumor Cells

Detection of tumor cells. Each day I drive to my hospital. So this is in summertime when I go to my hospital, this is a tree. And but when you look at the century and during wintertime, you see that. So this is of course our goal that we have the the tumor is disguised by the by the leaves in this case. So we would like to see the tumor cells being separated from the surrounding liver tissue. So this is something that you can also find in the book that you have the contrast kinetics in the tumor compared to liver tissue. You can see quite nicely that we have some tumors that enhance much earlier than the liver parenchyma, and much stronger, maybe also during a short or for a couple of seconds in the tumor. And then of course, it is being washed out very quickly. And others are enhancing also prior to the liver parenchyma, but not at the same level as the one that I was just talking about. Others enhance just like the liver parenchyma, but they lose a contrast concentration quickly, and others never take up the same amount of contrast bubbles compared to the liver parenchyma. So this is a normal situation and a lapse.

Example: Rectal Cancer Patient

So you look at a patient, this is a patient with rec cancer. Can we dim down the light, please? Oh, thank you so much. So Just have a look. So this is daily challenge. Are there any metas In gray scale? I must confess I didn't see anything. So I used contrast. And on the right side you can see contrast. And What is interesting to see, if you look at segment seven here, yeah, you see there's an area that is hyper announcing, and over a couple of seconds, just Three, four seconds, it started to wash out in the center. And then you can always see a hyper announcing river around it. So this measures eight millimeters inside stop. And then of course we can say, okay, do we really believe in that? Let's do it again. Okay, so now we have, you see now the washed out Lesion quite nicely. Then we give a Second injection in order to see is it really hyper enhanced the arterial face. Here it is. You can see the supplying artery. This is the tiny artery supplying this tumor. So this is something that you can see for let's say three, four seconds. But this is maybe an advantage to characterize the tumor. That is what we can do. This is the one that I was talking about. So this was an eyeopener for Me. So that was late in 2009 when we said we have to find a better technique to image contrast.

Example: Breast Cancer Patient Under Chemotherapy

So This is a patient under chemotherapy with breast metastatic breast cancer. So we were looking at the liver and we thought, oh yes, maybe there are multiple, maybe there's only a few, but definitely there are plenty changes In this liver due to chemotherapy. So we said let's look at contrast. And so this is what you can see now, a big metastasis and all the tiny lesions here that do not or that have been washed out are Metas. So we counted the number was over 50 meta, and most of them ranged between three. This is something that we could that We can see very nicely. CT was performed on that patient, and CT saw only a couple of handful of metastasis. So I think we are much more sensitive in most cases. If we have good scanning conditions, of course, that is the muscle. You can really see the liver quite nicely.

Example: Malignant Melanoma Patient

So this is a colleague of mine, she's 45 having malignant melanoma, and she was treated probably a little resected, and then she came back. And as then you can see very obviously she lots of metastasis in. But of course we also would like to know how they and what is the degree of of confusion in these Metastasis. Because this would be an argument to say what is happening under chemotherapy or under immune modulating therapy. Is the vascularization going down, yes or no? So we need to have a basic study on contrast. So this is what what we have here. And now you can see the contrast is arriving. You can see the arteries, Only the arteries, and now you can see lots and lots of your tests all vascularized during the early arterial phase. So this Is during the the first 10 seconds, you can see this metastasis. Okay? Then of course, we would like to know something about the character of the lesion. Of course, you just see is Of course a characterization of the metastasis each time that you detect in the passengers, no matter interest the face or the late face, it is also a characterization of the truth.

Characterization Example: Prostate Cancer

So this is by Gary Lawson. I like this. He said, this is how my Anderson may look happy or maybe suicidal or something in between or whatever. But the Anderson always looks the same. But if you could look deeper to his heart or his soul that there are different moods, but you don't see it. So there's exactly situation that you grace, you can never really see what is it? Is it really a tumor? Is it to be not tumor? You just have this tion. And that is of course, important. That is why we do need contrast. I give you examples for that. So this is a patient with a prostate cancer. This is the only lesion that we saw. The lesion is measuring six millimeters in size. You can see it here, the globe that has been removed. And you can see the lesion I think you can see it with the EPO rim and the echogenic center. And then we give contrast. And this is an accumulation mode. And the accumulation mode You can see very nicely, but single vessels arteries are entering the tumor. So it's being vascularized through this arterial phase. So this characterizes the tumor. And you can see they are more or less chaotic, more or less chaotic vasculature.

Example: Neuroendocrine Tumor

Well, here, this is a patient with a neuroendocrine tumor. Again, this tumor measures less than one centimeter. And let's have a look how it it is vascularized. Of course, we know that neuroendocrine tumors are hypervascular. You can see the supplying artery. You can see the hyper enhancement you in the arterial face. And again, what we are doing next is we use a accumulation mode. And I zoom the image. It's exactly the same, it's taken from the loop above. And this is how it looks like. And you do not only see the arteries, but you can now already see the shunts to the to the veins, to the portal vein. So they leave the lesions. So this is the reason for intrahepatic metastasis. Okay? So we see the the veins draining the tumor.

Example: Colorectal Cancer Metastasis

Or here's another patient with a calcium rate metastasis. And you can see very nicely the artery that is supplying this tumor. You can see that the tumor speed is taken up the contrast, and then it's starts to wash out already during the arterial phase, we now the arterial phase has been defined up to 30 seconds. And now you see we have now 26, 25 seconds, and it's starting to wash out. Okay? So this is a malignant tumor, of course. This is another case with iso enhancing tumor. The center is necrotic, as you can see here, and there's only a couple of seconds when you can see the tumor is iso enhancing. And then it's washing out very quickly. Now you can see it's washing out nearly completely. It's only a question of seconds. Or here, of course, on gray scale, you can say, oh, yeah, that's clear. This is a patient with a colon cancer. And you can see lots of metastasis, but it's not so easy to define where and how many metastasis are there. But if you give contrast, then you can see contrast is arriving. Then you again, you have a couple of seconds where you can see a slightly hyper enhancing lesions. You can see them here. You see the arteries being well defined from the portal veins that have a little bit less contrast filling. And now you can see they're washing out and then you can count them. So that is more convincing than the gray scale, I think, especially for follow up.

Example: Ovarian Cancer Metastasis

Okay, This is a ovarian cancer metastasis. And again, we look for the artery or the arterial enhancement. You can see that the center is again, ischemic, but what you can also see is some shunting to the periphery. So this is no tumor there, a tumor tissue. You could see it's wet shaped. And this is very often the case wet shaped shunting. And then you can see a little bit later, completely washed out in the late face, but still you can see some shunting effects here.

Example: Gastrointestinal Stromal Tumor

This is a gastrointestinal stoma tumor. And you can see very nicely in the slightly hyper enhancing tumor where the bubbles come from. They come from the periphery and they enter from the periphery to the center. And the center, again is ischemic. And what you can also see in the periphery, there are some satellite metastasis or tumors that is also typical for this tumor.

Example: Suspected Cyst in Malignant Melanoma Patient

And sometimes you have a grayscale image and you think, ah, clear case. It's just its cyst. So you can see this is a patient with a malignant melanoma. And I used different modes and then I switched to the linear probe. And on the linear probe, it was not really well round shaped. So this is why I thought, well, let's do contrast. Let's do contrast. So this is here, this is the so-called cyst. It's not a it's a tumor. It is a metastasis from the and it's not the only one. The next one is here, and next one is here. This one subcapsular measures four times two millimeters, and you can see the supplying artery of this tumor. And it's of course washing out quickly.

Example: Calcifications in Malignant Tumor

Cancer calcifications also clear finding on grayscale ultrasound. But as soon as you have the if there's a history of mal malignant tumor, you should perform a contrast study because this calcifications are calcifications of the tumor. So you can see during the arterial phase a hyper enhancement around around the tumor. This is hyper enhancement. This is the calcification. Of course, it's not taking enough contrast, but calcification is just in the center and around it, there's a tumor. So you should take time and contrast to evaluate if there's only a calcification of this, a calcified tumor.

Example: Wedge-Shaped Hyperenhancement in Colon Cancer

This is another patient who had a colon cancer, multiple metastasis. And you can see here a which shaped hyper enhancement of a subsegment in segment seven. And you can see it's hyper enhancing. You can see the metastasis as washed out lesions close to this area. And this is the loop. And when we look at the loop, very careful, and we look at the 19 second image and then we 22 seconds, and this is 28 seconds. And we look, these are the arteries supplying this subsegment, and they are responsible for the hyper enhancement. And what we also see is the portal vein between is occluded because of tumor and here as well. So this is something that we can see very nicely with contrast if we have and use a very high spatial and temporal resolution contrast setting.

Example: Highly Vascularized Colon Cancer Metastasis

This is also finding, this is also a colon cancer metastasis. And you can see very highly vascularized already on color doppler. And this is on the left side, the enhancement behavior of the tumor. Well, in the beginning it it starts to be well nearly well-defined, but then it's failing away. The contrast is being enhancing the area around the tumor. And on the right side, you can see the tumor is now washed out. So the idea was when we saw that, well, how big is the tumor? So you can measure it as the hyper enhancement around the tumor. Is that does that belong to the tumor or is it only shunting? And we think it's only shunting. We ask our pathologist after surgery, how does this tumor look like many metastas satellite metastasis, maybe? No, not, it's a very very well defined tumor. So this is shunting.

Example: Shunting in Another Patient

This is another patient also with shunting. And you can see very nicely this is the early arterial face where the tumor is enhancing. And then over time you can see the wash out and around. The wash out area is an area with hyper enhancement.

Example: Prostate Cancer Follow-Up

Okay, so this is a patient who had a prostate cancer four years ago, and the urologist was looking after him and one day he found out, oh, there is a lesion in the liver. I sent this patient to ct. CT says, yes, there is a lesion, but it's probably a benign lesion. But he recommended follow up after half a year. So half a year later he came back and then the ct report said, yes, there is still the same lesion, but it has become bigger. We suggest to do a biopsy or something else to characterize this lesion. So this is why the patient was sent to my place. And yeah, this is the arterial phase and it's a classical finding. You can see the central arteries supplying this area, and you can see arteries branching from these main artery into the tumor tissue. Okay, So we have no real neovascular. There is some neovascularization, but the major arteries are not destroyed. And you see it's starting to wash out. And if we look a little bit later, this is after one minute to 10, it is nearly completely washed out. So this is a typical finding for non-Hodgkin lymphoma. Not all non-Hodgkin lymphomas look like that to be to make that clear, but some of them do. And we biopsy this tumor. It's always interesting to go to the pathologist and have a look at it. So this is in the center, you can see normal hepatic tissue and around it you see tumor cells. And this is the PEX five stain staining the active B lymphocytes. So this is then the diagnosis confirmed, serious diagnosis of an extra hepatic non-Hodgkin lymphoma. There were no other lymph nodes in this patient C.

Conclusion

So thank you very much for your attention. So you see Sears is a strong diagnostic weapon.