CEUS of Focal Liver Lesions - HD

Introduction

I am Dr. Stephanie Ruth Wilson.

I'm a physician in Canada and I practice ultrasound
and have a very special practice focused on contrast
enhanced ultrasound studies predominantly of the liver,
but also of inflammatory bowel disease.

I'm a professor of radiology
and gastroenterology at the University of Calgary.

The talk that I'm going to share
with you today is an unusual presentation which I hope
you'll find educational and enjoyable.

And it's part of a case-based interactive session at RSNA
2013 in which I speak in a quiz format about the benefits
of contrast enhanced ultrasound for liver mass evaluation.

Today we're going to speak about contrast enhanced
ultrasound of focal liver lesions.

I'd like to make the disclosure
that the contrast agent used fin is off-label
for use in the United States,
although it is an on-label use in Canada where I live.

Objectives

So the objectives of this presentation are
to show the fundamental principles
of contrast enhanced ultrasound interpretation with regards
to enhancement patterns and vascular morphology.

And this will be presented in an interactive quiz format
with case presentations.

Contrast Enhanced Ultrasound of Liver Masses

So contrast enhanced ultrasound
of liver masses is the most successful pursuit
for contrast enhanced ultrasound
and this can be judged in terms of the number
of published papers and the ongoing clinical work
and research endeavors.

And so basically when we consider characterize the
contrast enhanced ultrasound of liver masses,
there are two questions which we can pose.

The first is related to liver characterization
or asking ourselves what is it?

And the second is related to liver mass detection
or asking ourselves the question.
Is it there?

So the first pursuit
that we undertook when we started
to use microbubble contrast agents was the development
of an algorithm for the diagnosis of liver masses on CEUS.

And so this is similar to those
for the non-invasive diagnosis of liver masses on CT
and MR scan, not surprisingly.

So these of course are based on the enhancement
characteristics in the arterial phase
and the portal venous phase.

However, contrast enhanced ultrasound has the added
advantage of temporal resolution
and also exquisite vessel morphology.

Washout and Malignancy Prediction

So the first question which I'll pose relates to washout.

So washout of a liver lesion in the portal venous phase is
highly predictive of which of the following,
A malignant tumor, a benign tumor, a lesion
of hepatocyte origin, a lesion of non hepatocyte origin
or a liver abscess.

So considering these five possibilities,
which one should you always think of when you see washout
of a liver lesion on CEUS?

Well the answer is a malignant tumor.

So malignant tumors have a high association with washout.

And so in the early work that we did, we found
that this benefit of portal venous phase enhancement was
really very significant in terms of characterization
of mass lesions in
that washout has a very high positive predictive value
of malignancy and sustained enhancement alternately has a
high positive predictive value of malignancy.

So if we look at this portion
of a schematic which we've created
to show the imaging features of benign masses
and metastases, you can see if we look at the column,
the third column, the portal venous phase imaging
that the three benign tumors listed at the top have a strong
tendency to still show enhancement in the portal venous
phase, whereas the metastasis comprising the group at the
bottom of the schematic.

Although they can have variable imaging in the arterial
phase, they have a constant period appearance in the portal
venous phase where they're shown on the schematic as black
or having shown complete washout.

Case Examples: Hepatocellular Carcinoma vs. Focal Nodular Hyperplasia

So let's look at that in another way.

So here's a 27-year-old male with hepatitis B virus.

If we look at the peak
of arterial phase enhancement on a contrast enhanced CT scan
and a contrast enhanced ultrasound,
we can see a concordant image with
a nonhomogeneous hyper vascularity of the mass
with a low attenuation area.

Essentially if we look in the portal venous phase,
however on both imaging again we see a concordant result
with washout of the mass.

So what does this mean?

It means that we should be suspicious
this is a malignant mass.

And the washout in the portal venous phase is
what is telling in this regard.

And this is a biopsy proven hepatocellular carcinoma.

So contrast this with another young asymptomatic woman,
we inject the contrast
and at the peak of the arterial phase we see a homogeneous
hypervascular mass on both the CT and the ultrasound.

In the portal venous phase,
we show sustained enhancement on both images
with a non enhancing scar
and this of course suggests a benign mass on the basis
of this sustained enhancement
and this is a proven focal nodular hyperplasia.

Case Example: Metastatic Carcinoid Tumor

So let's have another question.

A 60-year-old woman with a remote history of breast cancer,
she presents to the emergency department
with a right-sided abdominal pain.

She had a non enhanced CT scan on the basis of a suspicion
of a renal stone and
although she did not have a renal stone, she was found
to have an indeterminate mass in her liver.

After considerable further imaging,
she was referred for ultrasound.

So on her ultrasound we can see this echogenic mass deep in
her liver far too deep
to perform contrast enhanced ultrasound.

But in the left lateral decubitus position from an
intercostal approach, we can bring the mass much closer
to the transducer crystal
and it is in this position
that we do the contrast enhanced ultrasound shown here.

So when we inject the contrast,
you can see the mass is immediately hypervascular even
before the liver has enhanced.

However, as the liver progressively enhances, you can see
that the mass is no longer enhanced
and has now become black.

So if we look, we can see the mass on baseline in the
arterial phase at 11 seconds showing homogeneous hyper
vascularity and
by 22 seconds it has rapidly washed out.

So when we see this appearance
with wash out in less than 30 seconds,
what is the question that we'll pose?

So the enhancement characteristics of this tumor suggest
that we should recommend which
of the following a phasic CT scan,
a contrast enhanced MRIA biopsy, a mammogram
or a colonoscopy.

So obviously if you consider these possibilities,
the phasic CT scan
and the contrast enhanced MRI will both confirm the mass
lesion in the liver,
but they will not give us additional information.

We could do a biopsy to get the answer
or we could perform a mammogram if we were suspicious
of breast cancer or a colonoscopy if we might be suspicious
of a tumor of GI origin.

So the answer here of course is that the CT
and MR won't give additional information.

The mammogram and colonoscopy might give an
answer, but not likely.

And what we have to do is a biopsy.

So the correct answer when we see this rapid washout is a
biopsy of the tumor.

And so when we have this kind of tumor hypervascular with
that washout, we do the biopsy
and this is a metastatic carcinoid tumor.

We show also on
that ultrasound a small bowel primary tumor shown here
as a hypovascular mass arising from the bowel wall.

So what have we shown so far in the cases we've looked at?

We have established
that washout is predictive of malignancy.

Timing of Washout

So the next question relates to the timing of washout.

So the timing of washout of a liver lesion helps
to differentiate a a sarcoma from he angio endot thoma,
a peripheral cholangiocarcinoma from a metastasis,
a hypervascular from a hypovascular metastasis,
or a non hepatocyte tumor from hepatocellular carcinoma.

So what does the timing of washout actually help us with
Will it helps us with the differentiation
of non hepatocyte from hepatocyte based tumors
or essentially what we're considering is metastatic disease
or cholangiocarcinoma from HCC.

So this timing of washout exquisitely well shown on CEUS
is very, very valuable
for this most important differentiation.

So when we consider malignant liver tumors, we know
that timing of washout is discriminatory.

And in a study performed in my laboratory in Toronto some
years ago, we noted that metastases washout very fast
often within the timeframe of the arterial phase
and they tend to wash out completely.

And so if we come back to our schematic, we can see
that in the arterial phase shown in the box
at the bottom of the page.

These lesions can have variable morphology,
they can show hyper vascularity,
they can show rim enhancement
or they may show hypo vascularity.

But regardless of their appearance in the arterial phase,
in the portal venous phase, they show rapid
and complete washout.

Case Examples: Metastatic Tumors

So if we look at three different patients with
malignant tumors, we can see a rim enhancement pattern,
we can see diffuse hyper vascularity,
or we can show diffuse hypo vascularity.

Regardless all of these tumors here we can see two hypo
coic masses on the baseline scan.

And when we do the CUS,
again the masses have transient hyper vascularity and then
before our eyes these tumors wash out
as the liver begins to enhance.

So those are metastatic tumors.

Case Example: Cholangiocarcinoma

So let's look at the other side of this coin.

Here's an asymptomatic 68-year-old female
with a unremarkable liver apart from a large mass lesion in
the posterior aspect of the liver shown in sagittal
and axial plane.

So when we perform contrast enhanced ultrasound, we can see
that this mass is hypervascular immediately prior
to the enhancement of the adjacent liver.

So at 18 seconds the mass is hypervascular.

However, as we watch the mass, we can see
that the mass is now at 25 seconds beginning to wash out
and by 29 seconds the mass in fact appears black within
the enhanced parenchyma.

So if we look at still images taken from the clip,
we show the mass at 14 seconds is hypervascular,
but by 37 seconds the mass has washed out again,
rapid wash out in less than one minute
and by three minutes you can see
that the mass is completely black.

So we know that our differential diagnosis includes
metastasis or cholangiocarcinoma.

This is not hepatocellular carcinoma
and it's not a benign tumor.

So this is a biopsy proven cholangiocarcinoma.

So this rapid washout in one minute
or less, what should we think of?

We should think of metastatic disease
and we should think of cholangiocarcinoma,
although it may rarely be hepatocellular carcinoma,
this kind of rapid washout is much less likely
for this diagnosis.

Hepatocellular Carcinoma Enhancement Patterns

So let's go on now and talk about hepatocellular carcinoma.

So the classic enhancement pattern for HCC is that
of arterial phase hyper vascularity
with portal venous phase washout,
which is often slow and weak.

Now we know also
that there are many VA variations including in the arterial
phase, ISO or hypo vascularity
and in the portal venous phase slow or no washout.

Consequently, our schematic
for hepatocellular carcinoma is quite elaborate
as shown here.

However, if we concentrate on the issue that we're dealing
with, we can see that the portal venous phase variations
include hyper vascularity in the arterial phase
with no washout on the top line
or delayed washout on the bottom.

Case Examples: Hepatocellular Carcinoma

So let's look at such an example.

Here's a 73-year-old man from Hong Kong whose hepatitis B
virus surface antigen positive.

So when we look at him,
we see a very nice liver without any stigma of cirrhosis.

However you can see nicely within the center of the liver,
a well-defined mass.

When we inject contrast, we can see easily
that this is a hypervascular mass.

So we are thinking
of hepatocellular carcinoma when we see this
hyper vascularity.

Now when we look at the mass at the peak
of the arterial phase, we show the homogeneous vascularity.

When we look at one minute the mass is still
hypervascular relative to the liver.

When we look at two minutes, the mass is iso vascular,
it does not show rapid washout.

However, at three minutes we show rather weak washout.

This is classic hepatocellular carcinoma.

Let's look at another patient,
an indeterminate mass in a patient without documented risk.

So we don't know what this is, it could be many diagnoses.

And so we do an immediate contrast enhanced ultrasound at
the time of its detection
and we show again a homogeneous hypervascular mass.

So then when we observe the mass at one minute,
we no longer see the mass, it's iso vascular
at one minute 30 seconds.

The mass remains iso vascular.

So what does this mean?

Could this still be a malignant tumor?

Yes, it could indeed be a malignant tumor.

So what should we do? We should watch for a longer time.

And with the contrast agent that I use definit,
this is five minutes minimum for sure.

So when we look at three minutes
and 50 seconds, I'm sure you'll agree with me,
there's a vague suggestion
of washout when we continue observing
to four minutes, 30 seconds.

You can see that the mass has definitely washed out.

So there's our summation, arterial phase,
hyper vascularity, weak washout at four minutes.

Again, classic hepatocellular carcinoma
and totally different from the enhancement patterns
that we observed for metastases and cholangiocarcinoma.

So coming back to our question, the timing of washout
of a liver lesion helps to differentiate very importantly
non hepatocyte tumors from hepatocellular carcinoma.

Case Example: Hemangioma

So let's look now at a 59-year-old woman
with a recently diagnosed brain tumor.

She has an unexpected liver mass on portal venous phase CT
scan, which is quite indeterminate, sticks out of the liver,
has a heterogeneous appearance
and is of uncertain diagnosis.

When we look at this patient on baseline ultrasound,
we can see this unusual somewhat echogenic mass lesion.

Again, quite indeterminate on the ultrasound scan.

When we add color doppler we can see substantial blood flow
which might make us suspicious,
but again, it doesn't tell us the answer.

However, when we inject contrast on CEUS,
we can see a quite different pattern that we've seen
with the other tumors.

And so here we look at this clip
for some time at 1516 seconds,
the mass is enhancing some somewhat more.

And when we look at the clips,
the images taken from the clip, you can see these series
of images right up
until the patient has complete enhancement of this mass.

So the next question is the enhancement characteristics
of this mass suggest
what diagnosis an incidental heman genoma,
a focal nodular hyperplasia, hepatocellular carcinoma,
a metastasis or an adenoma.

And so here I'm sure you've got this
answer, incidental heman.

And this is of course characterized by peripheral nodules
of enhancement with centripetal progression
and sustained enhancement
and it doesn't have the linear vessels that we see with the
HCC and metastatic lesions.

So no further investigation is required for this mass.

So when we look at hemangiomas on ultrasound, they tend
to have an appearance such as this
where early on they're often quite hypovascular.

Then they start to show the peripheral nodules
as shown in the middle image
and ultimately more complete enhancement,
which may not be uniform as here where portions
of the tumor remain unenhanced.

Case Example: Rapidly Perfused Hemangioma

So what about this patient?

An oncology patient with an unexpected liver mass on
CT scan shown on ultrasound adjacent to the diaphragm.

And here on three images from CEUS,
we can see again peripheral nodular enhancement
with centripetal progression of the enhancement.

So when we look at the clip, you can see in this clip,
which is looping that the mass enhances very rapidly.

So this is a rapidly perfused hemangioma
with the peripheral nodules and centripetal progression.

MIP Imaging

So let's go on to our last topic that we'll cover today,
and that's MIP imaging.

So with MIP P imaging, we track the course of the bubbles
between successor frames
and it provides
for us a huge advantage in the arterial phase.

So because of the temporal resolution,
we can see vessel morphology.

So here you can see on the top right image
that we're looking at a normal liver, liver
with beautiful arborization of the vessels.

And on the bottom left we're looking at a patient
with cirrhosis with marked truncation
and tortuosity of these abnormal vessels.

And so only on ultrasound can we see this exquisite
resolution where here in a patient with a hemangioma,
we can see the normal vasculature with resolution up
to the six order branches of the liver vasculature.

So this maximum intensity projection
or MIP imaging contributes most to the differentiation
of which tumors metastases from hepatocellular carcinoma,
adenoma from hepatocellular carcinoma, f and h from adenoma
or peripheral cholangiocarcinoma from metastatic tumor.

While we know that metastases
and hepatocellular carcinoma are differentiated by the rate
of their portal, venous phase, washout adenoma
and hepatocellular carcinoma are differentiated on the basis
of patient history more than anything else.

And when we consider peripheral cholangiocarcinoma from
metastatic tumors, they are virtually identical
and are differentiated predominantly on history again.

And so where does MIP contribute?

It contributes hugely to the differentiation
of FNH from adenoma.

Case Examples: FNH vs. Adenoma

So let's look at the clinical situation
in which this occurs.

So the frequent dilemma occurs when we have a young
asymptomatic female with a hypervascular mass on CT scan
and we pose to ourself the question, is it FNH
or is it adenoma?

So contrast enhanced ultrasound shows vessel morphology
and direction of filling.

And so let's look here at a patient with a classic FNH.

So you can see the kidney at the back of the image
and you can see with the MIP imaging that the lesion fills.

And then when we destroy the bubbles with a brief burst
of high mi, the tumor refills showing the stellate vessels
and the centrifugal filling from the center
to the periphery of the tumor.

Now, although we can often see this stellate vasculature on
color doppler, this has never been proven to be reliable
as an accurate method of diagnosing FNH, whereas
contrast enhanced ultrasound with its classic appearance on MIP imaging is recognized to be a confident method for this benign diagnosis.

So contrast this with another patient,
also a young asymptomatic female.

And you can see this patient with adenoma has got instead,
filling from the periphery of the tumor
with very dysmorphic vessels, classic
for a liver cell adenoma,
and another patient with glycogen storage disease,
a superficial tumor showing again the filling
of the tumor from the periphery to its center.

So the last questions that I will ask, I'll just review is,
that this question of maximum intensity projection,
it contributes most to the differentiation
of FNH from adenoma.

Conclusion

So that is the conclusion of the presentation.

Thank you very much for your attention
and I hope that this was a good learning lesson about liver
tumors with contrast enhanced ultrasound.