Characterization of Liver Masses with Contrast Enhanced US: What Sonographers Need to Know - HD

Introduction

Hello, my name is Cindy Peterson
and I am going to be talking
to you today about characterization of liver masses
with contrast enhanced ultrasound
and specifically about what sonographers need to know.
I have been a sonographer at Southwood Imaging in
Youngstown, Ohio with Dr. Richard Barr for over 20 years
and we started doing contrast agent studies
with ultrasound in 1997
when FDA approval was granted for cardiology
and not radiology in the early two thousands, we continued
to do studies in an off-label manner and
therefore we have dosed thousands of patients.
It is that experience about which
I'd like to speak with you today.

Objectives

Our objectives of the program will be
to explain the mechanism of the action
of ultrasound contrast agents
and appropriate scanning techniques so they're understood
to help you understand the patient populations
who may benefit from contrast enhanced ultrasound
and to discuss liver lesion enhancement patterns using
contrast enhanced ultrasound.

The Journey in Contrast-Enhanced Ultrasound

This is a photograph from Holly Aala in Maui,
and first of all, depending on
where you are viewing this presentation,
it may not be sunny,
but more importantly, this represents to me the
journey in contrast agent imaging and ultrasound.
Those of us that have been using contrast agent
for years know that we have climbed the mountain
and worked with the equipment vendors to get the equipment
to the point that it is today,
and we are at the precipice with the approval
of contrast agents
for liver lesion characterization in the United States.
We have reached a new point in ultrasound
and if this is not adopted
and if people are not adequately educated,
I fear we're gonna fall off of this precipice.
That is my purpose in sharing this information with you.
I like to approach this in a who, what, where, when, how,
and why approach.
And we're actually going to talk about why twice.
The first why is, why am I talking to you about this today?
And the answer is
because FDA approval was granted in April of 2016
for the first ultrasound contrast agent
to be used in a radiology application,
which was the characterization
of focal liver lesions in both adult and pediatric patients.
This indication was followed later that year
by the indication for Vesco ureteral reflux imaging in
pediatric patients.

What Are Ultrasound Contrast Agents?

What are ultrasound contrast agents?
These are gas filled microbubbles.
They're smaller than the size of a red blood cell.
They have a lipid shell on the outside
and a gas in the core.
The gas depends on the particular agent that is being used.
Some of you might be thinking the same thing I thought when
Dr. Barr first said that we are going
to be using ultrasound contrast agents.
There have been a few times over my ultrasound career in
which a radiologist or another physician has told me
of a new innovation and I've literally had to stop
and ask what they were talking about.
The first of all was transvaginal.
For those of you that predate transvaginal sonography,
when you're first told we're going
to place a transducer into the vagina,
it seemed like a foreign concept,
but now it is standard of care.
The same thing is true with ultrasound contrast agents.
When I was told we were going
to be injecting air bubbles into a patient,
the radiographer in me became fearful.
However, if you look at the size distribution on this slide,
the microbubbles are smaller than the red blood cells.
Therefore there is no concern for the microbubbles
to become trapped in pulmonary circulation.
And the risks that we have with air emboli in other
situations do not occur here.
And in fact, in a paper
that was published about 10 years ago,
we can see the size distribution of both microbubbles
as well as red blood cells.
The red blood cells are denoted with the darker arrows
and the microbubbles are denoted with the white arrows
and we can see the size distribution
is actually very similar.
I also wanna draw your attention to the fact
that these bubbles are from the contrast.
Agent Sono view.
Sono view in Europe is the same agent
as Lumon in the United States.
It is the first agent to be approved
for radiology indications in the United States due
to the FDA request to change the name.
If you look at literature from Europe, you will find
articles about sono view as one of the agents being used.
It is the same agent as Lumon in the US
ultrasound contrast agents are injected intravenously either
into the inac cubital vein or even a vein in the wrist
or hand if needed.
These are blood pool agents,
meaning they circulate throughout the bloodstream
and they're not excreted into the collecting system
as CT contrast is.
As the microbubbles are circulating, they interact
with the sound beam and produce harmonic signals.
The oscillations of the microbubbles will increase the
signal noise ratio
and this nonlinear response
of the bubbles will produce harmonic frequencies.
Prior to having harmonic imaging as a standard
imaging package on our ultrasound systems,
harmonic imaging was used as a method
of contrast agent visualization and research.
When the approval for radiology was not granted,
the equipment vendors went ahead
with the harmonic imaging technology
and it became standard of care long
before contrast agents were available to us

Mechanism and Scanning Techniques

When the microbubbles oscillate in the sound field,
we can see on this diagram
that if we're using a very low energy or power
or a very low mechanical index,
there's not much oscillation.
We go to an intermediate mechanical index around 0.1.
We start to have some oscillations
and if those oscillations become so powerful
that the bubble actually bursts, we are not going to be able
to use that microbubble information
that happens when the mechanical index is higher.
That means that as sonographers we have to pay attention
to the mechanical index, which we typically don't do
unless we're doing obstetrical ultrasound.
This however, has already been
preloaded into the contrast packages
that are on the ultrasound systems.
Every manufacturer now has a push button
contrast software package
and when you enter the contrast software package,
the mechanic index automatically goes down to a level
that is acceptable, usually around 0.1 or just below that.
So we're going to keep the MI in this level
as we see in the orange box the safety profiles
of ultrasound contrast agents have been established.
There have been decades of patients scanned
and especially in the US the patients who have been dosed
for cardiology serve as a reference base as well.
There's a short half-life
of ultrasound contrast Agents typically lasting
around five minutes in circulation,
meaning we can use multiple injections.
If a patient has more than one lesion to be characterized,
we can do an injection and characterize the first lesion
and then either try to destroy the bubbles with a higher MI
or just wait for the bubbles to dissipate
and then perform a second injection.

Benefits of Ultrasound Contrast Agents

The why of ultrasound contrast agents answers a question
of why do we need contrast agents in ultrasound?
It is different than in cardiology
and cardiology contrast agents are used to help
improve a suboptimal examination that is not true
in radiology.
Ultrasound contrast agents do not compensate
for poor sonographic technique.
These are used to characterize lesions
and again, focal liver lesions in particular in adults
and pediatrics have been approved by the FDA as well
as looking for vesco terro reflux.
In pediatric patients, there are a number of patients
who cannot have CT
or MRI contrast either due to renal insufficiency
or if there is an allergy to iodinated contrast media.
In our practice, we have seen that these patients have
greatly improved ability to have diagnoses
by using ultrasound contrast agents.
The literature has shown that ultrasound contrast agents
are very effective both in terms of
sensitivity and specificity to characterize lesions.
When ultrasound or CT
or MRI have not characterized the lesion ultrasound contrast
agents can do this as well.
The cost of ultrasound is significantly lower than the cost
of either CT or MRI.
By adding in the additional cost of a vial
of contrast agent, which is currently reimbursable,
we still have a much lower cost margin
than if the patient were to be subsequently referred for CT
or an MRI exam.
In pediatric patients, the image gently directive says
that if there is a manner in which a patient can be imaged
without using ionizing radiation,
that should be the first imaging modality that is used.
There is no conscious sedation required for ultrasound
as compared to imaging modalities like CT or MRI.
Also, in addition, patients
who have undergone interventional procedures such
as radiofrequency ablations or cryo ablations
or microwave ablations
or endovascular stent repairs can be evaluated
with real time mechanisms to look for blood flow
and assure that the interventional procedure
has been successful.
Other ischemic defects such as infarcts
or transplants can be evaluated as well
and the real time assessment adds a dimension
that we don't have with CT or MRI.

Liver Vascular Phases

Before we talk about specific lesions, we need
to review the liver lobule.
Each liver lobule has six corners
and add each corner we have the portal triad,
we have a branch of the proper hepatic artery.
We have a branch of the portal vein and we have a bile duct.
Arterial blood is delivered to the liver through a branch
of the hepatic artery.
At the same time
that arterial blood has traveled down the aorta
and through the SMA
and IMA delivering blood to the intestines.
That intestinal blood then is drained
through the portal system.
So the second blood
that arrives at the liver lole is the portal venous blood.
This blood then is distributed throughout the hepatocytes
and so the third place in which the blood is delivered is to
the liver parenchyma.
This means that we have three specific phases on
contrast enhanced imaging methods.
In this graphic we can see that the
unenhanced image, whether it is CT or MRI
or even an ultrasound without color,
Doppler shows really no difference between the viscera
and the vessels immediately after injection.
We have the arterial phase
and we can see that we are going to have blood and
therefore contrast in the aorta in the hepatic artery.
Also in the mesenteric arteries in the splenic artery.
During the portal venous phase,
the portal veins will become apparent
as blood is draining into the liver from the intestines.
And then as that blood is distributed
to the liver parenchyma, we have the late phase,
which is also known as equilibrium.
Notice that the hepatic arteries
and portal veins are not evident any longer.
We can see the hepatic veins
and this parenchymal blush within the hepatic parenchyma.
This is the basis of a multiphasic ct.
On your left you can see a CT exam without contrast
and the center, you can see the arterial face.
So we can see hepatic arterial blood
and then we can see the portal venous structures
during the portal venous phase.
There is not a late phase reflected here.
Notice that in this patient's liver lesion we have a
difference of appearance on the phases
and different lesions.
We'll have different enhancement patterns which is the basis
of our ability to characterize these lesions.
If we can see this on ct,
we can see this on ultrasound as well.
Each ultrasound system
that has a contrast package has a timer
and we can see the timer in the corner on the system.
And this is a about 19 seconds
and 20 seconds after injection.
This is the arterial phase.
Here we can see the portal venous phase
and then in the late phase
or equilibrium, which is about two minutes
after injection in this patient, we can see
that we have parenchymal flow
and no apparent vessels,
particular vessels in this image.
These liver vascular phases have been
well-defined in the literature.
The arterial phase begins about 10
to 20 seconds following the injection of contrast agents
and ends about 30 to 45 seconds after the injection.
This depends on the patient's cardiac output
and their overall health.
The portal venous phase then commences about 30
to 45 seconds after an injection
and will last about two minutes after the injection.
At this point, we're into the late phase
or the equilibrium phase, which will persist as long
as the bubbles are evident.
Please do not worry too much about the timing.
If we have a patient who is 32 seconds post injection,
don't worry about which phase is this
patient in at the moment.
We're most interested in what's happening to the lesion
as we are examining the patient
and you'll see that as we look at some case studies.

Enhancement Patterns in Benign and Malignant Lesions

Benign lesions we're going to talk about include he angios,
focal nodular, hyperplasias, adenomas and cysts.
Malignant lesions we're gonna talk about are hepatocellular
carcinomas metastases
and we also in our pediatric population
will have hepatoblastoma.
And the one lesion that's not reflected on this slide
is cholangiocarcinomas.
And all of these have some similar features as we'll see
There was a trial that was published in 2008
that has a very nice graphic
to show us the enhancement patterns.
On the top of this slide we can see the benign lesions
and on the bottom of the slide we see the two most
common malignant lesions.
Focal nodule hyperplasias are often hallmarked by
what we call a spoked wheel appearance
or a stellate appearance.
This stems from angiography
and in this diagram we can see the central portion
with vessels that extend peripherally.
We can see this with contrast enhanced ultrasound.
Notice also that throughout the time
of enhancement this lesion's going to remain enhanced
and that's what this is telling us here.
Hemangiomas fill in from the outside in they have
centripetal enhancement.
This is reflected in the diagram as well
and these are the same patterns
that we can appreciate on CT and MRI.
But CT and MRI often don't capture
that spoke wheel appearance We see in an FNH
malignant lesions are going to take up the contrast
and then dump it off.
And if you think about the AV shunting
that occurs within a malignant lesion, that is logical
Metastases are going to have rapid enhancement often
with irregular vessels
and then that lesion is going to have loss of the contrast
or what we term wash out.
Hepatic cellular carcinomas have the same pattern.
Irregular vessels wash in
but the washout may be more lengthy
than what the metastasis.
The washout may take two or three
or even four or five minutes.
So it's important that we follow these lesions
for a longer period of time.
Benign lesions then are going
to remain enhanced in the late phase,
but what we see in the arterial phase
depends on the type of lesion.
If it's an FNH, we'll have central stellate filling
and if it's a hemangioma,
we'll have centripetal filling from the outside in.
In a globular fashion,
malignant lesions will have rapid uptake
with an irregular vessel pattern, relatively rapid washout.
However, the washout is more rapid
with a metastasis than with an HCC.

Practical Scanning Tips

Before we talk about specific cases, I want
to make a few practical points to orient you
to viewing ultrasound contrast images.
We're going to use low mi continuous scanning, meaning
that when we look at a dual image, the side
where we're going to view contrast looks
black prior to injection.
That is by design.
We're listening only for the harmonic signals in
that portion of the screen we're going
to use a dual screen in most cases.
To allow a point of reference, we're going
to place the transducer prior to the injection
and keep that transducer in a single plane.
That is very important to be able to characterize the lesion
and also for time intensity curves that we're going
to discuss later, we want to have
that lesion in plain meaning that as the patient breathes,
the lesion is still visible.
This is typically best achieved in a longitudinal plane,
occasionally an oblique plane.
We generally do not dose in a transverse plane
because as that patient breathes, the lesion will move in
and out of our field of view.
The cine clip length may be set for up to three minutes,
but we may need to image longer of patients
who have hepatocellular carcinomas.
Our field of view is not less than 10 centimeters.
This is to ensure that our PRF is low enough
that we're not bursting more bubbles than we need to.
And similarly, the focus is placed at the most posterior
part of the image, not at the area where you're examining
to keep from bursting bubbles unnecessarily.

Case Studies

Cysts

Going to look at a number of case studies.
We're gonna start with our benign lesions
and cysts are cysts are cysts
and we typically don't need contrast to determine that,
but if you have a cyst
that has echoes within it, contrast may be helpful.
When we look at a contrast enhanced image everywhere we have
blood flow will enhance as we see here.
We can also see the vessels
that have a greater concentration
of blood than the parenchyma.
Everywhere we don't see blood flow is going to appear
as black or koic.
This is koic not because it's fluid but
because it doesn't have blood flow.
That's going to be important to us in a few minutes.
Notice also that when we get down to about somewhere
between 12 and 15 centimeters,
we lose the resonance of the bubble.
So deep lesions are not well visualized with contrast,
we may need to put that patient into a decubitus position in
order to better visualize the lesion.
We don't see many occus cysts in our practice.
So I went to literature for this one
but this is not a typical cyst.
However, if you look at the contrast enhanced image,
the lack of flow tells us this is not live tissue.

Hemangioma

This patient has a hemangioma, she has a history
of a hemangioma
and this was a follow-up of her known hemangioma.
This has a typical appearance of a hemangioma.
We can see a well circumscribed lesion.
This is scanning subcostal.
This is scanning intercostal
and notice that the lesion is closer to the transducer
and will be easier to keep in plain when we're
scanning intercostal.
When we enter our contrast software package, you'll notice
that this side is initially black, that is on purpose.
And as we watch the contrast injection, the left side
of the screen in this package is going
to be optimized only for contrast.
This is the timer.
Every system has a timer
and at the completion
of the contrast agent injection in the beginning
of the saline flush, the timer is activated.
So we're gonna see this timer as we start.
So we are two seconds after an injection
and as I said, it takes about 10 to 20 seconds
for the contrast agent to arrive.
We can see a little backflow into the hepatic veins.
That means it's coming and now we can see flow into the
hepatic arteries.
So this is the arterial phase.
We can see the lesion
and by keeping the transducer in a single plane,
we can watch this lesion without the patient holding her
breath, we know that we're going to need
to examine this over a longer period of time.
So a breath hold is not going to be very beneficial to us.
Now we are in the portal venous phase.
We can see flow in the portal veins
and if we look at our lesion we can see
that we do not have enhancement in the center,
but we have this peripheral enhancement,
this centripetal gular enhancement.
And if you've been watching the lesion, you notice that
it is enhancing more as the patient is scanned
for a longer period of time.
This is a typical enhancement pattern for a heman
and hemangiomas will typically fill
over a period of several minutes.
If there's a small area of thrombosis,
we may not have filling in that area
and I'm not going to make you watch the entire three
minute clip, but you will see
that there is filling

Focal Nodular Hyperplasia (FNH)

Hyperplasias can be subtle lesions
and can be difficult to characterize with imaging.
This patient had a CT urogram
because she had had some kidney stones
and a liver mass was noted.
She was asymptomatic for liver disease.
Here we can see this left lobe ISO coic lesion
that's about three centimeters in size.
I put some calipers on here.
For us it is a little better seen in transverse
and in the transverse plane it actually measures
five centimeters.
Color doppler does not reveal anything that is very helpful
and those of you have scanned fhs know that typically
it is not possible to say Aha, here's an FNH,
but ultrasound contrast actually makes that possible.
So again, we're going to optimize our system.
So the contrast side is pretty much black.
We are seven seconds after injection right now.
So the contrast will be arriving and we can see flow.
Here's flow in the heart flow in the hepatic arteries
and I'm going to freeze this for a moment.
Okay, so our point of reference is right here.
The reconstructive B mode is never as high in quality
as the regular B mode image.
It is just not possible to do that.
I'm actually gonna back up our video just a little bit
and right here we can see the spokes of a wheel.
Okay, that is the stellate pattern that is characteristic
of an FNH.
It is a very short period of time
if you capture video clips.
However, you can go back and store stills
after the examination is completed
to acquire these very important images that are necessary
for diagnosis.
Sometimes it's easier to see those
after the exam is completed rather than
just watching in real time.
So as the contrast injection progresses,
we can see the lesion is remaining enhanced.
Okay, we're into the portal venous phase now
and this lesion is still remaining enhanced
and benign lesions will remain enhanced even
after the rest of the liver begins to lose some
of its contrast effect.
We are almost a minute post-injection now
and notice that the rest of the liver's starting
to lose a little contrast
but the lesions remaining enhanced.
That is typical for a benign lesion.
So here we can see at 35 seconds post injection
but even two minutes post injection,
the lesion is still enhanced compared
to the surrounding liver.
And this confirms to us this is a benign lesion.
It's that spoke wheel appearance that tells us it's an FNH

Adenoma

adenomas are less commonly encountered in ultrasound as
compared to fhs.
This patient had a history of oral contraceptive use
that was discontinued in 2014
and the reason she discontinued is
because she had severe right upper quadrant pain when a
right hepatic lobe adenoma had ruptured and was bleeding.
That mass was removed at the time of her surgery.
She had several other masses that were noted
and biopsied intraoperatively that were noted
to be adenomas as well.
She did not have a history of glycogen storage disease,
so this was termed hepatic adenoma.
Ptosis. She has several small
hypoechoic lesions.
This is the largest of the lesions
and this was a follow up on a known adenoma.
We can see about a two centimeter lesion close
to her diaphragm in transverse.
We can see this lesion as well.
We're not going to wanna dose this patient
transverse for two reasons.
Number one, the heart is very close by so we wouldn't want
to mistake any motion from cardiac activity and
have that show up in our mass,
but also transverse is not going to allow us to track
that lesion as much as we would like to.
There were other smaller lesions in her right lobe.
We can see these hypo coic lesions
that were also adenomas in this system.
The timer's going to pop up at the beginning of the clip.
It's going to be in the left lower corner
and this is three seconds after injection.
Our point of reference tells us we're looking right here,
we can see flow in her heart
and now we're going to see flow starting
to come into the liver as well.
So here's the hepatic arterial flow.
Here is our region of interest
and we can see this region is enhancing greater than the
surrounding liver parenchyma.
Notice that our focal zone is well below the lesion
that we are examining.
Okay? And as we transition into the portal venous phase,
we can see that this lesion remains enhanced.
The patient's actually holding her breath at the
moment, okay?
But we know that patients can't
sustain that for three minutes.
So it's better to use shallow breathing than
to have the patient hold his or her breath
and then have to do some catchup breathing.
As we continue to watch this lesion, we can see
that it has similar enhancement to the remainder
of the liver.
Adenomas do not remain quite as enhanced as FHS
And two minutes post injection.
There is no washout of this lesion either.
That tells us it's a benign lesion.

Hepatocellular Carcinoma (HCC)

Metastasis and hepatocellular carcinomas behave differently
than benign lesions.
On ultrasound contrast, this was a patient
who had an ultrasound of the abdomen ordered
for elevated LFTs.
He had no recent prior imaging.
He subsequently had a biopsy that showed
that this was an HCC.
Here we can see a large heterogeneous liver mass
in both a longitudinal as well as a transverse plane.
Colored doppler is not terribly helpful within the lesion we
do see what appears to be a large feeding vessel
in this lesion as well as patency of the main portal vein.
This is shortly
after injection, five seconds after injection.
This is a real life case
because this patient started to squirm
and you notice that transistor moving to make sure
that we're in the region of the lesion prior
to the contrast arriving, which we are.
And here we can see that large vessel
that we saw in color doppler,
but we have rapid enhancement of the lesion
and irregular vessels within the lesion as well.
There's a small amount of necrosis.
We can see that there's not really ever filling in
the center of this lesion.
And as we continue to watch this lesion,
we're getting into the portal venous phase.
Now that necrosis becomes a little more evident to us
if we had not been able to get back onto the lesion
with the patient moving as the patient is doing again here,
if we had not been able to get back onto
that lesion in time, we could perform a second injection.
That is a valuable tool in ultrasound contrast
that we don't have in other areas of imaging.
As we continue to watch this lesion, we notice
that there's actually more enhancement in the surrounding
liver now than in the lesion.
So we have some washout that is evident in malignancies
and in HCCs it can sometimes take a little longer.
So three or four or five minute intervals may be needed
to follow these lesions.
But the washout is evident here
and that's going to continue over time.
In fact, we are two minutes post-injection now
and there is obvious washout in the lesion
as compared to the remainder of the liver.
Very different from the benign lesions we just looked at.

Metastasis

Metastases have washout on ultrasound contrast as well.
This patient has known gastric cancer
and a new liver lesion.
She also has a very large right pleural
effusion as we see here.
Here is the solitary liver lesion we will be examining.
This is in transverse.
We're actually going to dose in longitudinal.
So here is this target lesion.
Notice that the left side
of the screen is intentionally black so we can listen just
for harmonic signals.
This is one second after injection.
And based on the patient's status
we may have a slightly delayed washing time.
This patient is ill, it's gonna take a little bit longer
for the contrast to get there.
We saw a little bit of backflow into the hepatic veins.
We know it's on our way, it's way, but be patient.
So here we can see the arterial phase.
There is no question where this lesion is
and almost as quickly as we have fill in, okay, we start
to have wash out of this lesion as well.
Okay? So we're continuing to watch this lesion, okay?
And notice that the center is becoming less
and less vascular, okay?
That is consistent with washout.
So we have to watch a lesion over a period of time
what happens in the arterial phase as well as
what happens in the portal venous phase
and in the late phase we can see within a minute though we
have characterized this lesion as being malignant
and if you look at the borders of the lesion,
almost the entire lesion has washed out.
After we have imaged the lesion
and characterized it, it is helpful to scan the entire liver
and look for other areas of malignancy
that we may not have known existed.
So we can sweep the liver.
We know that malignancies at this point in the injection are
going to appear as hypovascular or sometimes Dr.
Barrow refer to these as black holes.
So we'll sweep the liver to look for additional lesions.
This can be very important if the patient is going
to have an ablative procedure or surgery.

Quiz Case

Okay, now it's time for a quiz.
So you must play along at home
as you are watching this video.
This is a 45-year-old male
who had left sided abdominal pain.
He had an outside facility perform a CT without
contrast because there was a concern about a kidney stone.
That was what the referring physician was concerned with.
So he did not have anything wrong with his left kidney.
However we can see this lesion in the patient's liver.
It's about three by three and a half centimeters in size.
So this is a longitudinal image, okay?
In transverse we can see the lesion as well.
A little bit of posterior acoustic enhancement is visualized
and color doppler is not revealing the sensitivity
and specificity of color Doppler
to characterize liver lesions we know as exceptionally poor.
In addition, however, there is a lesion in his right kidney
that was not noted on the CT without contrast.
This makes characterizing this liver lesion now
of paramount importance.
The kidney lesion is about 2.7
by 2.4 centimeters in size
and will need characterized as well.
So 12 seconds after an injection is where we pick up
and our liver lesion is going to be in this region.
Okay, so we're looking around,
the contrast is just now arriving.
Okay? And here is the region of our lesion.
So think about what we just talked about
with the enhancement patterns, okay?
We're going to continue to watch this lesion
and again, keep the lesion in plain as the patient,
as the patient breathes so we can
get a fuller picture
of what's happening throughout the various
enhancement phases in the liver, the vascular phases.
Okay, are you coming up with a diagnosis yet?
Okay, so I'm going to stop our clip
for now and if we look at the enhancement pattern, we notice
that we did not have rapid enhancement,
but instead we have centripetal fill-in from the outside in.
So globular appearance to the contrast
as it appears this is consistent with a hemangioma
and in fact this is about a minute after injection.
We see this g globular appearance and this is a hemangioma.
Okay, this is three minutes after injection
and this lesion did completely fill in.
It took about five minutes.
In addition with a second injection
because we can do so, we characterize his liver lesion.
This is a hypervascular lesion.
This is 13 seconds after the injection.
This was a minute after injection by going back
and capturing this from a clip.
That's why there's the time differential here.
And this turned out to be renal cell carcinoma
as hypervascular masses do.
So it's very important to this patient
that we characterize his men correctly.

Performing the Contrast-Enhanced Exam

How do we perform a contrast enhanced exam?
We use harmonic contrast software
and different manufacturers use it differently.
We may use pulse inversion or phase inversion
or amplitude modulation.
The goal of all of these techniques is
to cancel out the fundamental information
and only visualize the harmonic signals that are produced
by the contrast agents.
The image settings in the abdomen are agent specific rather
than organ specific.
We have spent many years working with the manufacturers
to ensure that we have optimal settings.
And that is one thing that should not be a concern
for sonographers is the equipment settings.
We may need to modify these slightly depending on patient
body habitus or the lesion being examined,
but it is pretty much push button technology
for the most part now, which is really beneficial in being
sure that this can be implemented in a number of settings.
The initial settings in the exam protocols
are already established.
For the most part. As you can see, it's very important
to stay in one plane
and capture information
that can then be later examined in real time.
As far as how we can perform this in a radiology setting
and what we do in our practice, the patient needs
to be identified as to the need
for ultrasound contrast imaging.
The informed consent in our center is a verbal consent.
When the patient registers for the exam,
the patient will sign a consent saying
that they have been ordered to have an ultrasound
with contrast and they sign the same in the same manner
as patients who are having CT with contrast or MRI contrast.
The examination is then explained to them in the room
and a verbal consent is obtained at that time
the IV must be at least a 20 gauge if
absolutely necessary a 22 gauge has been used.
But if the gauge is too small, the pressure is going to
potentially burst contrast bubbles,
which would defeat the purpose of injecting contrast.
So we try to stick with a 20 gauge.
We activate the drug
and depending on the contrast agent we're using,
that can be done in different manners.
We are then going to use a three-way stop c**k.
We don't wanna use extension tubing,
especially if it's a small board tubing
because that can lead to bursting of bubbles as well.
This is a setup that we use in our setting.
We use a stop c**k
and wherever the stop c**k is pointing is
what is actually stopped or not flowing.
So we'll put the contrast on the straight portion
to deliver it directly into the vein
and then the stop c**k will be readjusted
and the saline flush will be delivered.
Here we can see the stop c**k.
We're going to perform a standard exam before injection
and localize the lesion.
It is acceptable to place a small mark on the patient's skin
to know exactly which plane you want to scan in.
We're gonna activate the contrast specific software
and activate dual screen in most instances
and then confirm the settings.
Be sure that we have low mi, which is
what the ultrasound contrast software should default to
and confirm that we have a three minute clip as well.
Performing a contrast injection requires two people.
The sonographer is going to be scanning
and that transistor needs
to be in place prior to the injection.
You saw how quickly the contrast actually
arrives at the lesion of interest.
So a second person is needed to perform the injection.
The person who performs the injection can be a nurse
or another imaging technologist or a resident or a fellow
or a radiologist.
It depends upon the requirements in your facility
and in your state.
So the contrast agent will be injected followed
by a saline flush.
We injected a rate of about one ml per second
and the same is true
for the contrast agent as well as the flush.
We're going to start the contrast timer at the beginning
of the flush and start our clip store.
We're going to save up to three minutes
and then we can do intermittent imaging
to watch he angios fill or HC HCCs wash out.
We're gonna collect data as long as needed for the patient.
Typically we're gonna stay in one position to begin with
and then perhaps sweep the liver.
We're gonna have that lesion in plain while the patient's
breathing and instruc the patient to breathe.
Shallowly, no deep breaths that would take
that lesion out of our field of view.
If we need another injection, we can do
that while the patient is with us and on the table.
If we don't, we can end the study
and then go back at that time
and acquire any still images we may need.
We can remove the IV
and the patient is discharged from the department.
The where and when are up to the facility.
Some facilities may have one day
that they do contrast studies.
That is what we do in our facility.
We have a single day per week dedicated
so the machine is already assigned
and the room is blocked for such things.
However, some facilities may decide to plan differently
and that is up to the facility.
Keep in mind however, when we talk about when
that there's a limited use of the contrast agent
after activation.
So you don't wanna activate all of the drug you might use
for the day in the morning.
It's best to activate that agent right
before you're ready to use the agent.
If you see any settling in the vial
and the vial does not look milky, you may have
to reactivate just
by shaking the vial just prior to injection.

Workflow and Team Roles

As far as who has what roles in
the exam, we're gonna talk about that.
As well. This is a paradigm shift for sonographers.
We are used to not dealing with IVs for the most part
and not dealing with contrast agents in a radiology setting.
This is not as much of a paradigm shift for radiologists
because they're already accustomed to interpretation
of both CT and MRI.
With contrast, sonographers are going to need to be familiar
with the scanning technique and the pattern recognition
and realize that this does add a short amount of time
to the examination.
We also have a non-invasive mindset.
Some labs even say non-invasive ultrasound lab on the sign.
That however, is a misnomer.
We have transducers that have been designed
to place in every body cavity.
We perform transvaginal sonography
and transrectal sonography
and those are certainly invasive type exams.
So an IV is no more invasive than any other types
of exams we already perform in our department.
There are models that we can draw from in cardiology
and some of these papers were published earlier in the
cardiology experience and some are more recent.
Contrast agents were approved in cardiology
at the turn of the century around 2000, 2001.
And the experiences from cardiology tell us
that there needs to be a team approach
and the medical director needs to be committed
to the quality of the contrast program.
The radiologist can work with referring physicians
to increase awareness of the fact
that this is a service being offered in your facility
and this will help increase the utilization of contrast.
The radiologist can also state in the impression
that contrast enhanced ultrasound may be beneficial in this
patient in the same way that he
or she would dictate that a contrast enhanced CT
or MRI would be beneficial.
The grapher must understand the equipment optimization being
that we use a very low mi
and again, this is part of the standard contrast package.
We need to realize that contrast will add time to the exam.
Once the workflow has been decided,
it does not add more than about five
to 10 minutes to the exam.
In most cases, we are responsible
for explaining the procedure to the patient,
possibly inserting the iv,
although in most settings that may not be probable.
If the sonographer does not have those skills,
even if the sonographer inserts the iv, we're going
to need an additional sonographer or nurse
or personnel to do the injection.
The sonographer must have the transducer in place at the
time of injection, so we're going to need availability
of other personnel to perform the actual injection.
That person only needs to be available
during the injection time, not during the entire exam.
In a more recent paper, Dr. Thomas Porter,
in speaking about the experience in echocardiography, said
that establishment of IV access remains one of the biggest
obstacles to administering ultrasound contrast agents in the
echocardiography setting.
This means that as labs begin to consider
implementing and utilizing contrast agents,
the workflow must be determined.
And whether that IV is placed prior to the standard exam
or during the standard exam depends on the facility,
but a lot of facilities have interventional radiology
procedure areas that could be utilized for this purpose.
There is currently reimbursement available for an ultrasound
of the abdomen with contrast for the administration
of contrast and a HPIC code
for the actual contrast material.

Technological Advances

I wanna talk about two technological advances that can help
in determination of lesion characterization.
The first of these is flash
and each manufacturer has a setting that is known as flash,
which is using a few frames of high MI technology
to briefly burst the bubbles
and watch the reperfusion of a lesion.
This allows us to look at a particular region of interest
and hopefully characterize it.
However, realize there's a limited number
of bubbles available, so we cannot use this technology three
or four minutes into the injection.
So here we can see the flash
and then notice the reperfusion of the lesion.
And in this lesion we'll wait until it flashes again.
Okay, we can see the spokes of the wheel appearance
and this is an FNH.
The other thing we can do is look at the contrast dynamics
or the time intensity curves that can be generated.
Similar to MRI, we can evaluate the profusion of a region
of interest and generate time intensity curves.
We're gonna go back and look at our patient
with the adenoma.
And this yellow region of interest is placed in the adenoma.
The green region
of interest is placed in the normal hepatic parenchyma.
And as we watch this, if you look at the bottom
of the screen, this line right here is
as time is proceeding.
So we can see the washing of the contrast right here. Okay?
And notice that both the yellow
and the green curves go up greatly
as the contrast has arrived.
And then as we continue to watch, We notice
that the region of the adenoma, the yellow
has a greater number of bubbles
or greater enhancement than the green.
So if, the interpreting physician does not trust his
or her own eyes to determine that this is a way
to quantify this, this may be helpful in therapies as well.
Most systems have this as an online on the system option,
and if it's not online, it can be done off
of the system on an offline computer.
Notice also, as I restart this clip,
that the motion tracking technology has become much
greatly improved over time.
So if the patient is breathing shallowly, the regions
of interest will actually follow the patient's breathing
to allow for better tracking of bubbles.
This is a benign lesion
and we can see that the lesion remains enhanced
and more greatly enhanced than the background liver.
If this were a malignant lesion, we would see washout
as we visually saw in the metastasis,
and that washout would be at a much higher rate than the
washout of the normal hepatic parenchyma.

Summary

In summary, contrast enhanced ultrasound can be beneficial
in a number of patients.
It does require a team approach
with the medical director being in support of the program
with the sonographer being knowledgeable about contrast,
and with the addition of other personnel
who can act in support roles,
especially in placing the iv in injecting,
there is a defined need for appropriate clinical education.
And I hope that this program has been helpful to you
in starting your journey toward using
contrast enhanced ultrasound.
Thank you.