CEUS in the Pediatric Liver: A Problem Solving Tool - HD

Introduction

Good afternoon everybody.

We, as Paul mentioned, we started using contrast enhanced ultrasound in children many years ago after following the success from what we experienced with the adult population.

We have a very large referral basis for children with chronic liver disease. We're a tertiary referral center for pediatric liver disease. In fact, the largest pediatric liver transplant center in Europe.

As everyone's aware, certainly from the adults, and it's no different in the pediatric population. Cellular carcinogenesis is a multi-stage process, and we are seeing these children sometimes three, four times a year, scanning them, looking for changes on B mode imaging in a very cirrhotic nodular liver, hoping to pick up early changes of HCC and malignancy, which is near impossible.

When you're looking at just b mode imaging, as I said, you have problems with gray scale imaging. These children are all predisposed to malignancy, but also in fact have an increase in the incidence of benign liver lesions as well. And you don't want to go put a child through major surgery or even transplantation when in fact what you're looking at is benign liver disease and not malignancy.

As Anna Maria alluded to, we obviously try and get away from the high radiation dose of certainly regular ct, serial ct, which unfortunately in the early days, we were being forced to use every time we picked up a nodule that had increased in size or changed in characteristics.

And there's also the risk of repeated use of iodinated contrast and more recently, as was mentioned in any of you who are at ECR and went to any of the pediatric sessions there, the repeated use now of IV gadolinium in these children, they're finding changes in gray white matter in the brain. So the constant use of these contrast agents we need to try and avoid as well.

Spectrum of Liver Lesions

These are a spectrum of the sort of disease, the nodules or focal liver lesions that we see at our institution.

Your benign lesions from liver abscesses, hemangiomas, adenomas, and even focal nodular hyperplasia all the way through to your malignancies, hepatoblastoma, HCC sarcomas metastases.

What we have to remember is, although these children have horrible looking cirrhotic livers, in fact, most of these lesions that we do pick up are in fact benign, and of all primary malignant tumors, less than 5% of these are secondary to liver disease.

Benefits of Contrast Enhanced Ultrasound

The benefits, as you would've heard in the last, over the last day and a half are we use enhancement characteristics of a focal target lesion. You'll see normal perfusion in lesions such as focal fatty sparing fatty infiltration, which we are seeing more and more of in the current population. And regenerative nodules.

You can certainly identify your benign lesions and also demonstrate your malignancies with early washout.

We first published our first set of data in 2013 where we followed up these ultrasound contrast ultrasound images with CT and MR and some of them also biopsy proven focal benign or malignancies. And from this we felt we were confident to then continue and extrapolate this to using it on a regular basis.

Regenerative Nodules and Focal Fatty Sparing

This is a child with a nodular heterogeneous looking liver, and you can see this focal lesion very well demonstrated on the periphery of the right lobe.

On the early arterial phase, the lesion enhances very much like the rest of the liver, and at four minutes there's no washout at all.

Children tend to hold onto the contrast for some reason longer than adults do. So you will find that in occasion you do need to be scanning up to five, six minutes to demonstrate whether there is in fact any washout of these lesions. And this is typical of nodular regeneration in a child with liver cirrhosis, focal fatty sparing.

Unfortunately, and as the press is continuously going on about, we are heading into an epidemic with children, overweight children, and we see a lot of these now, hepatic diffuse hepatic steatosis with these focal hyporeflective lesions.

Giving administering contrast will demonstrate absolutely no difference in the enhancement or wash out of these lesions. And as you see in adults with steatosis, this is focal fatty sparing.

In the early days, we did do MR to basically really prove to the clinicians that this was an ideal and optimal tool for imaging these children. Once we got around them and they started to believe what we were producing, we now no longer need to follow these children up with any further imaging.

Focal Nodular Hyperplasia

Focal nodular hyperplasia. Although rare in children, we do see quite a lot of here, particularly in the children who are referred to us with shunts, portosystemic shunts.

On gray scale imaging, you can see a very well-defined lesion with a central hypoechoic scar, which does show some color.

On color, Doppler arterial phase enhances at 23 seconds. On your venous phase, it's iso, a coke with the rest of the liver. And on your delayed phase 170 seconds, there is no washout. This is focal nodular hyperplasia or benign.

As again proved early on in MRI.

Hepatic Adenomas

The hepatic adenomas, again will show very avid enhancement on early arterial phase and no washout, predominantly no washout on delayed phase imaging. And again, as I said in the early days, we were supporting this with MR.

The joy of doing so. Loops with these sort of lesions is that very often, and I'm sure you heard this yesterday in the early arterial phase, you need to sometimes go back to differentiate how the enhancement pattern happened.

But unfortunately, the video's not wanting to show. Unfortunately, we can't always characterize whether these are adenomas or focal nodular hyperplasias.

We also now picking up a group of patients who are undergoing malignant change within these focal nodular hyperplasias. So even if you do identify a benign lesion, it is nevertheless important to go back and demonstrate on regular imaging that these lesions are not undergoing malignant change.

Hemangiomas

Children do develop hepatic hemangiomas, there's no magic age at which they suddenly appear. We have huge referral base usually from smaller peripheral hospitals, or in fact from GPs of patients children with well-defined hyper echoic lesions, which in an adult you wouldn't bat an eyelid about calling hemangioma. And for some reason in children we are a little bit more nervous about doing this.

But again, these show beautiful centripetal enhancement, and again, you can demonstrate this very easily in an ultrasound session with no need for any further CT or MR collaboration.

Infective Liver Masses

Infective liver masses. Most of these will be sent to you following MR appendicitis or incomplete treated appendicitis. As a result secondary to GI sepsis immune deficiency disorders, you occasionally will see amebic and I experience fungal infection, particularly in children with leukemia or other immune compromised conditions. And then on occasion parasites, you may be lucky enough to see the inflammatory mass in the right iliac fossa, but more than often you don't find an inflamed appendix. And typically the abscess usually occurs in the right lobe of the liver.

You will see the characteristic septated enhancement of the lesion on both phases with no indication that this might be underlying malignancy.

This was a child who presented with a very large abscess and you can see very beautifully demonstrated the enhancement of the septations.

What also is good with using contrast is that you can give the clinicians an idea of whether this is abscess is actually drainable or not on occasion. Just on B mode imaging, because of the degree of septation, it's very difficult to isolate how much fluid is actually present within the abscess and contrast artisan can clearly tell you, yes, there is a significant amount of fluid, you can stick a drain in this and shorten the child's hospital stay.

Undiagnosed Lesions

This was a child who presented to us with neurofibromatosis and on gray scale imaging, you can see very stenotic liver with these hypoechoic lesions. We were not sure what these were. We did do an MRI on her, which was unhelpful. We couldn't even see them on MR. Was this focal fatty sparing, could these be hemangiomas? We weren't clear. So we administered contrast.

And what we found was that on early arterial imaging, these were very avidly enhancing some slightly larger lesions on the periphery. These didn't demonstrate the typical centripetal enhancement of hemangiomas. And you can see at two minutes there was definitely no wash out of these lesions, possibly adenomas. We are not sure. Could this be neurofibromas? We still don't know.

To this day we just remain following her up. She has remained stable. These lesions haven't increased in size or haven't increased in number. Unfortunately, you can't always give people an answer. The clinicians weren't really happy for us to go and biopsy these, so at the moment she's just under surveillance.

Hepatic Malignancy

Hepatic malignancy unfortunately occurs in very young age group. We see them in infants as young as three months. Usually it's your children up to the age of three years. This is hepatoblastoma. These tumors are very large the time of presentation. They can be solitary, multiple multifocal, and the key is a child with an abdominal mass and a very elevated alpha fetal protein.

These children usually undergo chemotherapy first to shrink the tumor, and then followed by surgery either resection or transplantation.

This was the first hepatoblastoma we ever imaged with contrast ultrasound and you can see the very haphazard disorganized arterial of that lesion. And then on further imaging in the venous phase, the washout typical of malignancy.

This was a young boy who'd had a transplant for hepatoblastoma. And we still routinely follow them up, obviously looking at the transplant and trying to detect any recurrence within the transplant. And he presented with these hyper echoic focal lesions, which are actually lying within the duct. And the proximal rule loop, again, uncertain as to whether this was, could this be tumor? It's a very unusual place obviously for tumor to recur.

We administered contrast, and as you can see on the B mode, it is hyper echoic. It hasn't altered at all on the arterial phase and even on the venous phase, there was nothing to indicate that this was malignancy because he developed duct dilatation. Secondary this, he actually went and had a laparotomy. And these were found just to be inflammatory masses within the biliary tree. And proximal rule loop.

Hepatocellular Carcinoma

Hepatocellular carcinoma, they tend to be two peaks. Usually they're very young around the age of a year. And then in the teenagers, and these will arise from mature hepatocytes as in the adult population.

The caveat to them being in cirrhotic livers is that you do get an entity of fibrolamellar hepatocellular carcinoma, and these are non-cirrhotic livers. So you can get de novo teenagers age 14, 15, 16, presenting with these liver masses, normal parenchyma, but a large liver mass, which lands up to be an HCC.

Children with thalassemia are at large risk of developing HCC and are under a very strict surveillance program here. And this was a case. You can see this liver nodule on the periphery of the left lobe enhances at 16 seconds. At 58 seconds, you can start to appreciate the washout. And then at three minutes, this is definitely malignancy hepatocellular carcinoma.

As I mentioned, fibrolamellar HCC in your teenagers. And this was a lesion showed enhancement around the periphery of the lesion. On the arterial phase, this is possibly an abscess, but after fact centrally there is necrosis. There was some filling in on the venous phase and then wash out on delayed imaging. And this was a fibrolamellar HCC on biopsy.

Ultrasound in Older Children

Ultrasound. Again, in the slightly older population, if you have a teenager that will let you pop a needle in, when they come, just for your routine ultrasound referred by a GP is often very helpful.

This was a young guy of 17 who presented with right upper quadrant pain. GP thought possibly, did he have gallstones? Was there something else going on? And we found this hyporeflective well-defined lesion in the periphery of the right lobe, non-cirrhotic liver, nice and smooth. Could this be an adenoma? Could this be a hemangioma? We administered contrast, and you can see there's a large feeding vessel. We thought, oh, great, this is gonna be an adenoma. But as we kept scanning, in actual fact, there was washout, and you could see at one minute 30, there is washout within this lesion. And this was a malignancy.

Hepatic Sarcomas

Hepatic sarcomas can present in many ways. This was a child who presented actually with a history of right upper quadrant pain and fevers on b mode imaging. We thought, oh, this looks like an abscess. You've got a beautiful thick wall to it. Central necrotic lesion.

Color doppler showed peripheral color, possibly an abscess. We administered contrast. And I think what is important that you need to keep looking at those areas that are enhancing while you're performing. The contrast is that, yes, there is early arterialization within the wall of this lesion, fairly thick walled lesion. So again, this could still potentially be an abscess, but as you went on two minutes, 54 seconds, you can appreciate the wash out within the wall of this lesion.

And this in actual fact, we did go onto biopsy, and she had a sarcoma in characterization.

Mesenchymal Hamartoma

This is a mesenchymal hamartoma, this age group, you usually will be able to pick these tumors up. They young kids, infants, they have very enormous cystic tumors within the liver. And what you see is enhancement within these very thin septa within the lesion. There is absolutely no washout at all. And this is mesenchymal hamartoma.

Metastatic Disease

Meta disease in the general pediatric population is far more common than primary liver malignancy. You usually know that there's an underlying malignancy somewhere else. And often this is just surveillance scanning.

These are the type of primary tumors which the children will present with wilms, neuroblastoma, sarcomas, teratomas, and then lymphoma leukemia.

This is a typical picture of a child with a neuroblastoma. You're not gonna miss this metastatic disease, multiple focal lesions, but see how much easier it is to pick up these lesions in a child with a heterogeneous liver. And what we tend to do is give the injection and after about 40, 60 seconds, then start scanning. And what you see is these are these punched out holes. And this is typical of metastatic disease.

Other Applications

Moving slightly away from liver malignancy. We find that the more often you use contrast the braver you will get in saying, oh, well, let's see here. Let's try it here. Let's see if this works.

And this was a case, she was a 14-year-old. She was the daughter of a obstetric consultant who had right upper quadrant pain, had an ultrasound and she had in the gallbladder these lesions or these focal masses really sitting within the wall or sitting within the lumen attached to the wall of the gallbladder.

We don't see children very often with gallbladder polyps. Yes, inspissated bile and all. Absolutely. So could this just be, we thought, could this just be inspissated bile stuck to the wall of the gallbladder? And we gave a contrast. Matter of fact, surprise, these were enhancing very avidly. This is at 15 seconds. So these are small little arterialized lesions. In fact, she went on and had her gallbladder removed and these were gallbladder adenomas. So certainly worth doing at the time of her initial scan.

Conclusion

There's a huge spectrum of pathology in children with focal liver lesions from your benign to malignant characteristics.

The ideal thing of using contrast enhanced ultrasound is that you can image the three phases, real time imaging. You're not putting the children through a CT scan or MRI, taking a snapshot, hoping that you will catch the contrast as it goes through at the right time. You can actually watch these lesions in all three phases. It's a dynamic process.

The most important thing, certainly with our group of patients that we see is that detecting the early washout, which signifies malignancy.

It's comparable to enhanced CT and MR. Certainly in the pediatric population, we can use it by the bedside in a very ill child, and you only need very small doses of contrast.

There's a massive reduction in radiation exposure, particularly in those children that are on surveillance programs, whereas I mentioned we scanning them up to three, four times a year. Not ideal to be putting them through a CT or MR. Machine every time you pick up a change in a nodule.

Thank you.