Ultrasound Contrast: Principles and Applications - HD

Ultrasound Contrast Agents: Principles and Applications

Hello, my name is Sheila.
And I'm today going to discuss ultrasound contrast principle and applications.

Ultrasound contrast agents are new, exciting development
that we can start using here in the United States.

And they basically are microspheres
and the one that are approved for a contrast
for the liver
and some other application in the United States called Luon bico.

And basically what they are is they are micro bubbles
who contain inert low solubility gas,
so usually sulfur hexa fluoride,
which is contained within a phospholipid shell,
which give them some stability.
They're very small diameters, as you can see here.
And therefore they can easily pass
through the long capillaries.

So when they're injected intravenously in the circulation,
they stay in the capillary bed.
And an important to, important thing to realize is
that they remain intravascular, unlike CTO Mr.
Contrast, where there is no interstitial
or equilibrium phase,
but they do remain intravascular for several minutes.
And finally they're excreted
by the lungs after several minutes.

How They Work

Those micro bubbles are echo enhancers,
and this is due to changing acoustic impedance
between the bubbles and the blood.
And those micro bubbles, when they're insolated,
they resonate or oscillate,
and they're non-linear reflectors or,
and they oscillate at the fundamental frequency,
but also at multiple harmonics of the fundamental frequency.
And of course, as we go up in the harmonics,
there is decreasing intensity,
so the normal image at the second harmonics,
which gives you enough intensity to be able to detect it.

Technical Points

Now, another important technical point is
that when we image those micro bubbles, we need
to image at low mechanical index to avoid rapid bubble destruction.

So how do we do it? We image at the second harmonic,
as I said, and we use a pulse inversion imaging technique,
which I'll discuss in a minute.
And that allows us to image only the bubbles
and not the surrounding tissue.
So it's like a subtraction technique.
And this allows to improve a signal to noise ratio.
And we can do the subtraction technique when we match,
with pulse inversion imaging,
because the bubbles have a non-linear response at low mi,
whereas tissue have linear response.
So that allows us to visualize small vessels
with very slow flow,
and we can compare the acoustic enhancement in the lesion
or the area of interest to the surrounding tissue.

So this is how a pulse inversion imaging recovery works.
So we send a normal pulse and we send the inverted pulse.
And then what is image is the sum of echo.
So because the tissues have a linear response,
then the sum of the echos is zero,
whereas the bubble have a non-linear response, and
therefore the, they, they are, they have positive imaging,
and hence the subtraction technique.
So the tissue without bubbles will appear black
and the bubbles we'll be able to see.

So because of that, we basically need to have low,
we image at low MI as you can see here,
and we need a dual screen
where you will have your gray scale image for reference.
So we know what we imaging, especially when we start
before the bubbles arrive in the tissue, this part
of the screen will be completely black.
And then we image the this portion of the screen
with the pulse inversion technique so
that we can image the bubbles as they arrive.

This patient had a hypodense mass that was
somewhat difficult to see,
but really stands out with contrast imaging,
as you can see here.
And this is the gray scale image.
This is this patient GT scan, again,
showing a hypodense mass in the region of the hepatic hylum,
which was a cholangiocarcinoma.
The patient also has some ascites, as you can see here.

Advantages of Ultrasound Contrast Agents

What are the advantages of ultrasound contrast agent?
They're not nephrotoxic,
and they have a different allergy profile than Iron
United agents.

So in addition to that,
they really allow real time evaluation.
So we can see continuous visualization
of small blood vessels throughout the injection cycle.
There is a very high temporal resolution, unlike CT
or mr, we can only image a certain given points in time.
Here you can image continuously for several minutes.
We also have a high spatial resolution,
so we can see septations, small nodules, of course,
just like anything in an ultrasound,
there's no ionizing radiation.
We can also perform multiple injections,
at least two if needs to be.
And in general, they have a lower risk
of major contrast reaction compared to the CT OMR contrast agents.

Limitations of Ultrasound Contrast Agents

So there are some limitations,
however, they are the same limitations as ultrasound.
So we need a good baseline exam.
And really, if we don't have a good baseline exam
with gray scale, then your imaging
with contrast is not going to be that great
because the contrast cannot overcome the limitation
of basic gray scale ultrasound.
They do not, just like anything in ultrasound,
we don't have global imaging, so we really need
to focus on the region of interest.
This cannot be used for full body staging.
The way we can use CT or mr, it is operator dependent.
And there reimbursement issues at
least in the United States.
And finally, at this point, at least in the adult,
for intravascular use, FDA
so far only has approved contrast for ultrasound,
contrast for liver imaging.
But many of us have included ultrasound contrast
for off-label use for many other applications,
which I will be discussing.

Contraindications

There are some contraindications.
It used to be that cardiac shunts were contraindications.
This now has been lifted, so it's no longer the case.
There is an FDA black box warning, so
that the patient, we require that the patient stay 30 minutes
after contrast administration for observation.
And you need to have a crash cart in the area.
And of course, the patient needs an iv established before starting.

General Applications

So let's talk about general applications
and then we'll go more into a specific application.

It's used, it's very useful
for characterization of masses in patients
who have renal insufficiency and
therefore cannot have C-T-O-M-R contrast.
It can also be used in patients who have allergy to IV contrast,
and patients who cannot get r for example.
We've used it and some others have used it as well for in preparation for ultrasound guided biopsy,
if there is a large mass as is aquatic,
you can target the area of enhancement.
Sometimes the lesion on gray scale may be difficult to see,
and the contrast will help with lesion detection.
It can be used for characterization
of a lesion incidentally found on ultrasound in patients who have known masses to for follow up
to limit the number of ct and mr.
And finally, you can also use it to monitor response
for chemotherapy in patients who have cancer,
use a target lesion
and see response to contrast
to monitor response for chemotherapy.

Practical Tips

So how do we do it?
I wanna give you some practical tips.

So the first thing we do is you need
to get a gray scale
and color doppler ultrasound for baseline.
And as I said before, you need to have a good,
a gray scale baseline to make sure
that you see the area of interest.
Well, you also want to scan in a way that you can have the lesion
and the surrounding tissue for comparison.
Because basically what you're doing is comparing the
enhancement in the lesion to the enhancement
of contrast in the surrounding tissue.
You also want to be able to do it where the patient has quiet breathing.
Because if you only see a lesion when the patient has
to hold their breath, you
wouldn't be able to, the patient wouldn't be able
to do it for a very long time.
So all these things you need to do,
and you need to spend a lot of time
before you start the contrast
to make sure you have a good baseline exam.

We need an iv, as I said,
and ideally you want at least a 20 gauge needle so
that the bubbles when they go
through the needle do not break.
You need a three-way stopcock for the saline flush.
And I'll show you example that in a minute.

So the contrast comes in a little kit where in the vial there is powder and you have saline,
and you basically, you mix the saline
with a contrast agitate for at least 40 seconds
to resuspend the bubbles.
And then once a contrast is ready, you wanna make sure
that you select the contrast mode on your scanner.
And so you need to have the software to be able to do contrast imaging.
And what we do is we inject a 2.4 ccs
of the micro bubble solution, followed
by five cc saline flush, and we start real time scanning
and the timer with a start of injection.

So really it is a two people's job.
One person at the scanner, the other person is injecting.

This is what the setup would look like.
So I start, there's the same patient
that are cholangiocarcinoma.
So I start with a good gray scale imaging,
and I can see the lesion.
I have enough surrounding liver tissue to be able
to compare the contrast within the lesion
to the rest of the liver.
And I also want to notice
that when we go into contrast mode, which is here
because we're imaging at low mi,
then the gray scale image is somewhat degraded.
You, this is a much poorer image compared to this one.
And so you, and then here's the contrast image.
So this is how the your screen will be set up when you start contrast imaging.
And of course there is a timer that you know that go that is somewhere on the image.
So you can see what's going on with time.

This is just how here's the bubble.
The powder is here.
You are injecting the the flow,
the saline here, this is what it looks like.
And then you start just agitated
and you just shake it with your hands.
You can stop just like that.
And then the result is this kind of milky powder,
and you really have to shake it well for about 40 seconds.
Or you wanna make sure that the powder that the content of the vial here becomes
milky, and then there is no residual.
You've done a good job when there is no residual
white powder at the bottom of the vial here.
And then you withdraw the contrast in the syringe that is provided.
And then here's the three-way stop.

So the iv will go in,
the patient is connected that way.
So another little tip is that you want
to put your contrast syringe straight so that the
bubbles don't have to have this acute angle here.
And you put your five cc or 10 cc saline flush here.

So once you start, you start injecting.
Once you've injected 2.4 ccs, you turn the stopcock away from this area.
And towards this area you inject five cc,
which is the saline push,
which basically pushed a small amount of contrast you've injected through the
patient's IV into the patient.

Applications in the Liver

So let's talk about some applications.
Now when we'll talk about the liver,
which is a very important application, as I said,
this is the one that's FDA approved in the United States.
And again, it's this the indication
that I've already discussed.

So characterization of mass in patients
with renal insufficiency
or contrast allergy in preparation
for ultrasound guided biopsy.
It's also helpful for lesion detection
or characterization of a lesion.
We found incidental on ultrasound.

Now is that helpful for lesion detection?
It's questionable.
Now the contrast does stay in the liver
for about five to six minutes.
So theoretically you have time to scan the entire liver and
looking for liver metastasis
for non malignancy, is that good enough
for screening HCC?
We don't have enough information yet
to really answer this question,
and again, monitor response to patients who have liver metastasis after chemotherapy.

Hemodynamics of Contrast in the Liver

So let's review the hemodynamics
of contrasting the liver.
So it's very similar to what we do in ct.

So there is the hepatic arterial phase,
which starts at approximately 10 to 20 seconds
after the start of injection and last up to 40 seconds.
This is followed by the portal venous phase, which starts from 40 seconds to 120 seconds.
And then there is a late phase of bubble clearance.
And the contrast will be in the liver
for about five minutes.

Now, remember, unlike CTO mr, there is no interstitial phase.
And the contrast is the bubbles stay all the time in within
the liver vasculature.

So here's an example of a relatively normal liver.
So this was a 30-year-old male
who had acute liver injury,
and his liver was very heterogeneous
and was unclear whether this was just
because of his acute liver injury,
or potentially he could have mass.
So I'm just gonna fast forward this video clip a little bit.
And here you will start. This is the arterial phase, okay?
You can see contrast going within the hepatic artery here.
And as we keep going, we are moving
to the portal venous phase when there is now very good
enhancement of the entire liver parenchyma.
'cause remember that 75% of the blood flow
to the liver comes through the portal vein.
So this is now portal venous phase,
and you can see the liver parenchyma
and the vessels within it.
And you can see here that this is homogeneous enhancement
of the entire area.
So this was just a heterogeneous liver,
but with no focal masses.

Benign Liver Lesions

So let's talk about some benign liver lesions.

So hemangiomas are very common.
Typically on ultrasound they are present
as a well-defined echogenic mass.
And occasionally though,
you can have an atypical presentation.
So this patient where there is an hypoechoic mass in
the liver, but note that the border is echogenic, okay?
This is an atypical hemangioma.
If this was tumor, usually in tumors, the peripheral,
the periphery of the tumor is hypoechoic.
Okay? Here the peripheral of the lesion is echogenic, okay?
And just like what you see in ct, you will have centripetal progressive enhancement
with progressive filling in and nodular enhancement,
and the lesion progressively will become either iso
or more echogenic than the surrounding liver.
And there is very importantly sustained persistent
enhancement in the portal venous and delayed phase.

So peripheral nodular enhancement that is progressive.

So let's look at an example.
So this is a patient who is 46 years old,
has an incidental mass found on right upper
quadrant ultrasound.
And if you look at the mass here, it's a good location
for hemangioma, good appearance,
well-defined echogenic mass.
And so instead of recommending some other imaging, we can
quickly we inserted an IV injected contrast,
and this is what we see.

So I've just had a video clip of selected images,
but when you start here, maybe I will show
slow the clip a little bit.
You had see that you have nodular peripheral enhancement
that is increasing at time goes on.
Okay? So this is a typical appearance
for a hepatic hemangioma
that this patient did have a CT for some other reason later,
and it confirmed that this indeed was a hemangioma.

Another benign lesion
that is found often incidentally is focal nodular
hyperplasia, which is basically a pseudotumor,
which is a normal liver surrounding an arterial scar.
It may be rather difficult to detect at least on ultrasound, on gray scale,
because it's normal liver point mass.
So it has a almost the same echotexture the rest of the liver.
But sometimes you can detect it if you see the central
scar as you can see here.

So this is a nice example on ct.
Typically these patients have early arterial enhancement in the hepatic arterial phase,
and you can have early arterial
enhancement of the central scar.
Sometimes you'll see a large feeding artery
and there is progressive centripetal enhancement.
And then the enhancement persist in the portal venous phase
and kind of at one time will become iso intense to the rest of the liver.
And very importantly,
there is no washout in the portal venous or late phase.

So early arterial enhancement is very characteristic
of these lesions.

So this is an example from the literature showing intense
arterial enhancement with a big feeding vessel here
and the central scar.
And I will show you an example that we had.

This was a 47-year-old woman,
and you can see here that there is a on the mr this T2 bright lesion here
with a suggestion of a central scar.
It's on the portal venous phase
of the MR is iso intense to the liver.
And so here we did an injection,
so we'll just look in this area here.

So you can see that on the gray scale we don't even see
the lesion very well.
I'm just going to advance the video clip a little bit,
and here we'll study arterial phase the contrast coming in
and look in this area.
Okay, this is arterial phase
and there is early arterial enhancement of this lesion way
before there is an enhancement of the rest of the liver.
Okay? So this is brightly enhancing in the arterial phase homogeneous lesion.
Here in this particular case,
we don't really see a central scar.
And as we progress, we're starting the portal venous phase.
And you can see that the lesion now is barely
more enhancing than the rest of the liver.
And if we pursue this,
and usually in the liver, I will image up to five minutes
to make sure there is no delayed washout, then you can see
that it becomes isoechoic to the rest of the liver.

Another benign tumor adenoma,
which are often heterogeneous
because there is intratumoral bleeding.
We all know that these are more common in women who are taking oral contraceptive
or sometimes male who will take anabolic steroids.

So again, there are hypervascular on the arterial phase,
there is centripetal filling in on portal
vein and delayed phase.
And typically there will be no washout on the delayed
phase, but some can have delayed washout,
in which case they would not be able
to be differentiated from hepatocellular carcinoma.

Okay, another lesion
that can mimic a pseudo lesion that can mimic a lesion,
focal mass is focal fat.

So this was a young boy that had was kind
of large and had this
hyperechoic mass in the left hepatic lobe.
And so prior to biopsy,
we gave contrast.
And you can see here that it's basically enhancing
just a little earlier than the rest of the liver.
But then it becomes isodense in the portal venous phase
and also in the delayed phase.
And this was proven
to be focal fat on ultrasound guided biopsy,
and as a subsequent MR as well.

Malignant Liver Lesions

So now let's move on to malignant lesions.
We'll first talk about hepatocellular carcinoma.

Typically these will have, these are hypervascular
with strong enhancement in the arterial phase,
or you may be able to see a basket
of irregular arteries feeding the tumors from the outside.
Very importantly, they will wash out,
but their washout can be relatively slow and only start
after 75 seconds, and the washout can be variable.
So poorly differentiated HCC will tend
to wash out earlier than well differentiated HCC.
And rarely there is no washout,
but that's very uncommon.
And because they have this delayed washout, you really need
to image the liver with contrast for up to five minutes.

So this is an example from the literature, a hypervascular
mass with a large feeding vessel.
Let me show you a couple examples. We had.

So this was a 27-year-old male who had this very large,
lobulated hypervascular mass on the M mod.
You can see that the mass is
hypervascular in the arterial phase.
Compare the of the to the rest
of the liver parenchyma, there is a large central scar.
And so this would be suspicious
for a fibrolamellar hepatocellular carcinoma.

So this patient came for biopsies
and this is the hepatic arterial phase prior to the biopsy.
So I'm just gonna again, advance a little bit.
And you can see here the arterial phase
of the contrast is coming in
and you can see, you only see a part of the mass here,
but you can clearly see that is hypervascular compared
to the rest of the liver here.
Okay? Then in the early portal venous phase,
it's still enhancing similar to the liver,
maybe just a tad more than the liver.
So we keep going, this is a still
image here, so we'll keep going.
And then on the delayed, very delayed phase, this was
as like after three minutes, you can see here that the rest
of the liver is enhancing more than this mass here.
So there is some washout,
and that is why you really have to be concerned about hepatocellular carcinoma.
And this was a fibrolamellar hepatocellular carcinoma when we did
large core biopsies to this mass.

This is another example, a subtle hepatocellular carcinoma.
So on gray scale,
there is this echogenic mass note is the hypoechoic rim here,
which would make you worried
that this is a malignant lesion.
And then these are just selected images from a contrast enhancement.

So this is the early phase, and you can see this subtle.
Here's the bulge here,
and you can see this subtle hyper, it's hypervascular
or hyper enhancing on the early phase, this kind of
iso enhancing on the early portal venous phase.
And on a very delayed phase, I had to wait till about four
and a half to five minutes to see
that there is some washout.
Here. Again, here's a lesion.
And on the gray scale on the contrast,
you can see the subtle washout.
And this biopsy was a moderately differentiated
hepatocellular carcinoma.

An example, another patient we had recently
who has a it was a,
he came from the emergency department,
he had worsening ascites.
You can see that he has ascites,
and he also had what appeared
to be a thrombus in the portal vein.
So in these patients, of course, we have
to decide is this a tumor thrombus is a bland thrombus,
and it can be very difficult on gray scale.

So we gave him contrast. And here's the portal vein here.
So we'll see. Again, I'm gonna advance a little bit,
and here the contrast is coming in
slowly in the portal vein.
Here it is. Okay. And this is the arterial phase.
And then the portal venous phase is filling.
You can see there is a filling defect here,
but if you look here, okay, this tumor thrombus,
this is enhancing.
So if this thrombus is enhancing,
then this is actually a tumor thrombus.
And you can see there is very heterogeneous enhancement
of the liver parenchyma region.
Okay? And so you are very concerned
that this patient has a kind of a multifocal diffuse hepatocellular carcinoma
with a tumor thrombus.
And in these patients we recommended an AFP just
to check that yes, AFP was elevated.
And so he decided to go for hospice care.
This patient was unfortunately very sick,
but, so this presumably is a multifocal hepatocellular carcinoma with tumor thrombus
that is very nicely demonstrated with contrast.

And here is, again,
is CT again showing the enhancing thrombus in the portal
vein here.

Metastasis will have rapid
wash out in portal venous phase.
So even, and because metastasis are supplied by the hepatic artery,
even hypovascular metastasis oftentimes will have early
transient peripheral hypervascularity in
the early arterial phase.
If they're hypervascular metastasis,
then they'll have early intense enhancement.
Again, the important thing is there'll be a washout in the
portal venous phase, and usually it happens rapidly by 30
to 40 seconds.

So this is a unfortunate young man who came
to the emergency department
because he was feeling poorly.
And you can see from the CT scan why he was feeling poorly.
He has a liver hypodense masses.
He has a very large necrotic retroperitoneal mass here.
He has big masses in the mediastinum as well.
He is in the lung here.
We had a testicular ultrasound that basically showed
no focal mass, but this many many metastases.
And so he came to us for biopsy.
And here's his on the arterial phase,
you can see there is early intense peripheral
enhancement of this mass.
And so again, we biopsied the peripheral enhancing rim
and this was unfortunately metastatic seminoma.

So another example where this patient had metastatic breast cancer.
Now, in this patient, the lesions were really,
really difficult to see, she was coming to us
for biopsy on gray scale,
and we are giving her contrast here.
And you can see on the portal venous phase,
you can see here these hypodense masses, they're kind
of subtle, but at least you see them.
So we're gonna be able to use this to do the biopsy here.
And again. So this is a patient,
she had many lesions.
They're somewhat, you can see them,
but they're somewhat more difficult to see with gray scale.
And we really use our map from the contrast enhanced
where they look hypodense in the portal
venous phase compared with the liver to do the biopsy.
And this was metastatic breast cancer.

Summary for Liver Applications

So in summary, for the liver, the washout is really,
really very important
because washout is associated with malignancy.
So if you have rapid washout it metastatic disease,
usually delayed washout in hepatocellular carcinoma.
And in this paper here out of 147 Hypervascular lesions,
you had washout in 97% of malignant lesions.
They had some, there is some overlap.
They also saw washout in 36% of benign lesions.
So some of which were abscesses or focal nodular hyperplasia,
and usually importantly, a lack of washout in the portal
venous and delayed phase usually indicates a benign lesion.
Most of these are iso or hyper enhancing
compared to the normal liver.

Liver-Specific Limitations

So there are liver specific limitations.
If there are very deep lesions,
lesions high in the dome, there may be difficult
to see on gray scale and
therefore the contrast will also be very limited.
If the patient has more cirrhosis, there is
so much attenuation of the sound waves that again,
the contrast will not be very good.
Same if you have a small shrunken liver with limited
ultrasound window.

Renal Applications

Okay, so now I'm gonna move on
and talk about renal applications.

So again, important to remember, this is off-label use,
so therefore we get informed consent with a patient.
It's very easy.
You I just tell the patient, it's the same,
it's approved for the liver.
The contrast act exactly the same way.
We're just gonna put the probe on
the kidney instead of the liver.
And patients readily agree.

So what are the indication again, characterization
of an indeterminate mass in patients
who have renal insufficiency or contrast allergy
or an indeterminate lesion on C-T-M-R.
When there's a single phase,
and we don't know if it's a hyperdense or a
or solid renal mass, it's also very useful
for characterization of renal cystic masses
or determining if a renal bulge is a normal column
of Bertin, which was enhance the same with the rest
of the kidney or is a focal mass.
Or we can use it to evaluate renal perfusion
possibly in transplant, for example, to detect
potential infarct.
And again, just like in the liver in preparation
for ultrasound guided biopsies.

Hemodynamics of Contrast in the Kidney

So what is the hemodynamics of contrast in the kidney?

Well, you'll have rapid cortical enhancement in the arterial
phase from 20 to 40 seconds
after the start of injection.
That's a corticomedullary phase
where the cortex is enhancing,
but the medulla is still hypovascular.
And then later on from 40 to 120 seconds there is filling in
of the renal medulla.
So you have a nephrographic phase when there is homogeneous
enhancement of the entire renal parenchyma.

Now remember, there is no excretory phase, unlike
iodinated contrast,
and the contrast washes out of the kidney
after approximately three minutes.
So basically I image the kidney for three minutes.

So here's a normal renal enhancement, here's a kidney here,
and we'll see the contrast coming in.
You can see here the contrast coming in.
So this is a corticomedullary phase
where the renal pelvis is a hypodense compared to the rest
of the renal parenchyma.
And then progressively we are gonna move to the nephrographic phase where there is homogeneous enhancement
of the entire renal parenchyma.
And the only thing that we see
that is not enhancing is the collecting system
and the renal sinus fat.

So that's normal. So a very,
very good application is in a patient just like this.
Is this lesion that was detected on a gray scale ultrasound
in a patient who had renal failure
and was in the cardiac unit.
Is this a complex cyst or is it a solid mass?
And so this was very easy to do actually.
You can do it portably, which is a big advantage.
We went to the cardiac unit and this is the early phase
and this is the late phase.
You can see here the renal parenchyma enhancing.
And you see there is absolutely no enhancement
of the internal content of this lesion.
And therefore this confirms that this is a complicated cyst
and it is actually more elegant
and faster to do than an mr.

This patient had a non-contrast mr,
and again, the MR was actually indeterminate.
I'm not exactly sure why they did the mr
'cause we told them you didn't need to do this.
This really give you a very elegant
and quick answer as opposed to this patient.

So this patient on MR has this complex looking cystic lesion.
Again, this patient could not have contrast
because he had chronic renal disease.
And if I start this video clip again, here's a contrast coming in.
This is the liver. Actually, you see the mass here
and you can see here that there is enhancement
of the solid component.
Here's the kidney, here's the enhancement.
Okay, so it's also helpful
because we were then able to target
directly the solid enhancing component of the cystic mass.
And we were able to prove with biopsy that this was
a renal cell carcinoma,
likely a papillary renal cell carcinoma, was how it was signed out on pathology.

Limitations in Renal Applications

So there are some limitations, however, in large lesions.
So this is a patient who had a very,
very large mass in his right kidney.
Also, he already had a left nephrectomy
for renal cell carcinoma,
but the cystic mass in his right kidney was enlarging.
He had an elevated creatinine.
So you have a very ugly looking mass here
with all this solid appearing component.
So when we give him contrast, you can see these are selected images from the contrast.
There is no enhancement of this portion.
So basically this is just old blood.

And so the patient also had a ct, however,
and on ct, again, you can see the internal content
of the cystic lesion much better on ultrasound.
But what we did not see on ultrasound is
that there was a tiny, tiny component
of nodule enhancement here in it is in the arterial phase.
Here it is in the coronal.

So this could be a cystic lesion with a tiny renal cell carcinoma possibly,
because of his renal condition.
So we call this at least Bosniak III
because of this condition he was just followed
and at least this lesion as well
as this nodule was stable at six month follow up.

Now for solid renal masses, they will have different enhancement compared
to the renal parenchyma at least on one phase.
'cause remember, they don't have a normal nephron.
If it's the classic clear cell renal cell carcinoma,
you'll see a hyper enhancement.
The papillary renal cell carcinoma,
just like on CT will be a hypo enhancing early
look for pseudocapsule.

There's some challenges.
It's difficult to differentiate other solid masses such as angiomyolipoma who can have slow wash in and wash out
and oncocytoma.

So here is an example of a 62-year-old male
with an elevated creatinine.
He has this very large mass arising from the right kidney
here, you can see here this mass in the lower
pole of the right kidney.
So at the time of biopsy, we gave him contrast,
and again, we knew this was cystic.
So you can see that there is hypervascular enhancement
of the periphery of the lesion, but the center is necrotic.
So we were able to just biopsy again the periphery
to make sure that we could get good viable material.
And this was a classic renal cell clear cell carcinoma.

This is a small echogenic mass.
So here it is somewhat difficult
to see on the gray scale and we'll see on the arterial phase.
Just look here as the contrast arrives
here it comes.
And you could see here that there is early
and transient hypervascularity of that mass.
Okay, so it's very subtle, but it's there.
And so this again was a classic clear cell
renal cell carcinoma.

Now in this patient there is a hypo enhancing mass
with some calcification in the right kidney.
Here, here it is on gray scale.
And with contrast,
I just give you selected images in the arterial phase.
The corticomedullary phase, the nephrographic phase.
Here's hypo enhancing.
Here's a biopsy here.
And this was a chromophobe renal cell carcinoma who
which was hypo enhancing on the arterial phase compared
to the rest of the renal parenchyma.

Another example, very large mass
in the center of the kidney.
You can see it's hypo enhancing on the ct.
The arterial phase or mass is here on gray scale.
And again, multiple selected images show that this is the
mass is hypo enhancing even compared
to the rest of the kidney.
And this was a papillary renal cell carcinoma.

Other Potential Renal Applications

So there are other potential applications.
You can potentially use contrast to look
for acute pyelonephritis to identify renal abscesses or infarct.
It has been used to evaluate transplant perfusion or planning for biopsy.
I just showed you.
And finally, it is approved to look for reflux in our children in this case of course
to inject contrast within the bladder
and look to see if there is reflux
of contrast within the ureters.

Other Applications

So some other applications that have been described in the literature.

So preparation for biopsy
or ablation, looking for enhancing component, you can do
that in any kind of tumor.
And it's also helpful for follow up after ablation
'cause you should have no enhancement of the tumor
if it has been properly ablated.

It has also been used for inflammatory bowel disease, such
as Crohn's disease to look
for active inflammation.

So this is just an example of a patient
who had a very large GIST tumor,
a young woman
with this very large mass in the abdomen
and again, prior to biopsy
because we wanna make sure that we want
to minimize the number of biopsies we do and get our best map for where we should get the core biopsies.
We look for enhancement in this lesion.
And you can see again, here's the on the contrast coming in
and again, peripheral enhancement.
So we used this area to obtain our core biopsies
and this was a GIST tumor on biopsy.
And then at subsequent surgery.

I've also used it in the spleen.
You know, really you can use it
for soft tissue tumors, et cetera.

This is mostly for research purposes,
but you can do a quantitative analysis
where you do time intensity curve, where you place an
region of interest in the tumor as well
as the adjacent organ,
and you can compare the enhancement of the tumor
with the rest of the organ.

So this was the fibrolamellar hepatocellular carcinoma I showed you earlier.
And in the liver you can see there is earlier enhancement
compared to the liver and then washout.

Conclusion

So in conclusion then,
ultrasound contrast is really a powerful tool.
In well-selected cases there are some obstacles.
First of all, the limitation of ultrasound.
Also practice patterns, at least in the United States.
Reflexively people will order CT, MR
and don't think about ultrasound contrast.
I think ultrasound community really are obligation to educate our clinician to the potential
of this technique and their issues with cost
and reimbursement.

And I thank you very much for your attention.