CEUS in Renal Diseases - SD

Introduction

My name is Hans Peter Sco.
I am an internist,
and I started to do ultrasound in the year 1982.
And with contrast agents,
I did the first studies in 1996.
At that time, we had LEVU as the agent,
that was followed by a second generation agent, some
of you in 2001.
So I'm now head of the central ultrasound department in
the Silva Hospital in Hanover, Germany.
And we are performing a lot of
ultrasound studies,
roundabout 17,000 a year.
And the major interest that we have is of course,
interventions, contrast agents.
So we are performing all kind of
studies except cardiac examinations
and O ob GYN examinations.

The Role of Contrast Enhanced Ultrasound in Renal Diseases

The topic of my talk today is seals in renal diseases.
And what is the role of a contrast enhanced ultrasound?
Is it maybe tumor detection?
Well, generally not
because we used to use a gray scale imaging
for detecting renal tumors,
but there are certain circumstances under which we would also use a contrast agent
for the detection of renal tumors.
Second is, of course, the characterization of lesions.
And we know that the vessel density of tumors,
of malignant tumors is a prognostic factor.
So the question is, do we benefit from using Sears?
The third is staging.
Staging is not only a matter of contrast,
but we definitely use gray scale imaging for detection
of lymph node metastasis.
And when it comes to organ metastasis, then
of course we use contrast again.
For example, for looking for liver tumors
or metastasis follow up is important,
because the follow up means that we look for
the contralateral kidney
or even the ipsilateral kidney.
For looking for recurrence of the tumor.
Trauma is something quite new to the ultrasound.
The ultrasound because so far we have not been used
in contrast agent in trauma so often.
This is because patient with severe trauma,
they are first referred to ct study,
because CT can really detect the severeness of the trauma
and the damage to the kidney.
So no surgeon would only rely on contrast enhanced ultrasound.
But there are many blunt trauma
and especially the follow up.
And here, especially in the younger patients
where contrast agent plays really a role
and has reliable
and gives reliable clinical data, infectious diseases.
I will come to that. And this is also a new field.
And I have some examples of that
that I will demonstrate later.
It should be mentioned that the use of so review is off-label when it comes to the examination
of the kidney, So the
detection of renal tumors.

Tumor Detection

So we know from older studies like this one from Jamie Sinal from 1996,
that ultrasound is not the imaging modality
that gives us the best detection rate of renal tumors.
This is a comparison between CT and ultrasound.
And it correlates the size of a lesion to the detection rate.
And you can see that below 25 to 20 centimeters, ultrasound is already not detecting all the lesions and it's going down.
And even when you look at ct, CT
below 15 millimeter in size, cannot detect all the lesions that are smaller.
So this gives us an idea why ultrasound is not
that perfect in detecting focal renal lesions.
So this is a patient with a breast cancer,
and she underwent CT study before,
and CT studies said, well,
we see a metastasis in the right kidney,
so this is the right kidney in the two scan planes.
And the question is, do you see the tumor?
And I have to confess, I didn't see the tumor.
So we added contrast.
And by adding contrast, you can see this is a cross-section,
study of the right kidney.
We used oh 0.8 ml of cell of view.
And here you can see quite clearly the lesion.
And it is not that small.
It is a little bit more than two centimeters in size.
And this is the longitudinal plane, second injection.
And here you can see a hypo vascularized tumor
of the right kidney.
Okay, it is maybe even more interesting to look at the patients with a history
of renal cell carcinoma
because we know that there is a certain number of cases in which these tumors arise in the contralateral kidney.
Like here in this patient,
he has underwent nephrectomy 10 years ago due to an RCC.
And gray scale ultrasound detected at least two lesions that you can see quite clearly
on the o both scan planes.
So the question was,
is a nephron sparing surgery still possible in this patient?
And this was the question, not only of the patient,
but also of the urologist.
So we studied this patient,
and you can see each lesion
that you can see on the right part of the image that is
dark, that is hypovascular, represents a metastasis.
So we counted 17 in this loop
and histology detected altogether 22 rccs.
So a nephron surgeon sparing surgery was not possible anymore.

Characterization of Lesions

Real tumors and statistics, I show you some numbers
that are quite interesting.
One is regarding the tumor size and its character.
We know that lesions below one centimeters are
mostly benign, not mostly, but round about 50% are benign.
And if you look at lesions exceeding seven centimeters in
size, only 87% are malignant.
But what is much more interesting is when you look at the
outcome after imaging modalities have been applied in these patients.
So there is one study showing that 376 patients
who preoperatively have been diagnosed
with malignant lesions, intraoperatively,
and by histology only 21% or
or 21% were benign.
So this clearly shows that there is a,
a deficit in the imaging modalities in making a reliable diagnosis
what the character of a focal liver le, focal renal lesion is.
So compared to CT and MRI, does CS provide an equal
or high diagnostic confidence?
I'm sorry for this image, it's an image that is,
comes from a cartoonist from Germany,
and it obviously looks quite critical upon radiological examination techniques.
So what is the challenge that we are facing?
Number one is, does CS help in differentiation in the
differentiation of solid tumors, benign versus malignant?
What are the predominant early solid lesions?
It's the RCC number one.
And can we differentiate RCCS from
real metastasis?
Can we differentiate RCCS from a ML, from lymphoma,
from Oncocytoma, omas, and other tumors?
So this is the question,
and I give you some of the examples.
First of all, what entities do we face?
In rccs, there's number one,
70% are clear cell carcinomas.
They have a relatively poor prognosis, are characterized
by a high vessel density,
and characterized genetically by a suppression
of the P three gene responsible for the suppression
of neovascularization.
Then 10 to 15% are represented by papillary,
rccs.
They have a slightly better prognosis
and they have a lower vessel density.
The chromophobe RCCS have the best prognosis.
They have a very low vessel density,
and very seldom are the duct Bellini carcinomas,
making up 1%,
and they arise from the collecting duct tumors.
Okay, So this is the typical finding on grayscale
image of a renal cell carcinoma.
You can see some necrotic areas within the tumor,
and the tumor is exceeding the renals.
And this is the color Doppler image.
You can see only very, very few vessels,
within the tumor.
And if you look at the CS examination,
you can clearly see why that is the case,
because blood flow is slowly,
and the vessels are very tiny,
and they come from the outer part
of the tumor going to the center.
And you can see within the tumor
that the vessel density is changing.
In the center of the tumor, there is a lower vessel density
expressed by a lower enhancement level.
Okay, This is a female 60-year-old,
and you see that there is a tumor in the right kidney
as well as in the left kidney,
but both have a different gray scale appearance.
The tumor on the right side is apor.
It is more ac rich on the left side.
So the question is, are they both the same
or do they differ?
So this is turned out to be an RCC on the right side,
and you can see quite nicely a hyper vascularized tumor.
And over time you will see that this tumor is
washed out, like here.
This is after one minute roundabout.
Okay, And now let's look at the left side.
So this is color doppler on the left side.
And again, in color doppler, you only see vessels
that are surrounding the tumor,
but you do not really see intra lesional vessels.
So when we add contrast, you can see
that this tumor is indeed vascularized,
and you can see the arrival of the contrast bubbles,
and slowly the tumor is filling
and completely filled after a couple of seconds.
And this tumor was also removed
and it turned out to be exactly the same type of tumor.
So the grayscale image appearance does not
predict anything.
So real clear cell carcinoma was the diagnosis on both sides.
The papillary renal cell carcinoma is less vascularized,
as you can see on the image,
a contrast image on the right side,
you can see an early arrival in the normal renal parenchyma,
and very slowly you can see an enhancement of the tumor,
and this tumor is washing out quite quickly.
This is another example of a patient that was diagnosed
by CT and by Sears as an RCC,
but histologies said it was an oncocytoma,
it was not a malignant tumor.
And here you can see the appearance after 14 seconds.
You can see after 14 seconds, it is nearly,
not enhanced.
After 24 seconds,
you can see some vessels in the tumor.
And the vessel is maximum enhanced after 29 seconds.
And after 50 six seconds, the tumor is washed out from contrast agent.
This looks similar, except that the genicity
of the tiny tumor
that is measuring 11 millimeters, and this tumor is apor,
but the contrast behavior is the same.
And this was a papillary renal cell carcinoma.
This is a bigger tumor measuring maximum size
was six centimeters.
And you can see
after nine seconds an enhancement that is of the tumor
that is less enhanced than the renal parenchyma.
After 15 seconds, you have an ice enhancement
between the tumor and the renal parenchyma, and
after 28 seconds, it is slightly washing out.
And this was an oncocytoma.
So seals as a conclusion cannot reliably differentiate
between solid renal tumor entities.
So this is another patient with the hematuria.
And what you can see in this patient is a small
and moving solid lesion in the renal pelvis.
And it, of course, the question was, is this clot
or is it really a tumor?
And given contrast, you can see that it was a
urothelial carcinoma.
It takes up contrast as you can see it here.
So it's a hyper vascularized tumor that is moving under the,
urine production.
This is, of course, easy to diagnose from gray scale image, you can see a huge urothelial carcinoma invading the renal parenchyma.
And giving contrast, it might be a problem
because the ceal carcinomas take up
or are highly vascularized
and take up contrast comparable to the amount of enhancement that you see in the renal parenchyma.
Have in mind that our contrast agent is a strictly intravascular agent,
and it's not being extracted in the,
urinary tract.
So after nearly two minutes, you can see
that the tumor starts to wash out,
but it is not that clearly
as in the other tumor types
A ML and contrast enhanced ultrasound.
We found out,
AMLs may be hyper vascularized iso vascularized
or hyper vascularized compared to the renal parenchyma.
And we have not found any specific criterium
that allows us to differentiate AMLs from other solid renal tumors.
So other, any indications for using seals in a ML?
We think there are, first of all, let us talk about,
how reliable conventional ultrasound performs in
diagnosing A ML.
There is a meta-analysis
that was published in 2007 by farelli.
And in this meta-analysis,
220 hypoechoic noncalcified renal lesions were
examined, and the prevalence of a ML was 45%
sensitivity was oh 0.99,
but a specificity of only oh 0.43.
So these are not very good results,
although the majority of people are doing ultrasound, think that making the diagnosis of an am ML is an easy job,
but I think it is not,
because one third
of the renal cell carcinomas when they're small
are also hyper coic.
So far, there's no evidence
that seals will increase the diagnostic confidence in
characterizing a ML.
But how do other imaging modalities perform?
And I told you
before, we have round about 20%,
misdiagnosed rccs.
So this is a study published by Tokai in 2004,
and you can see that these are tumors that are diagnosed
as RCC and are referred to a center
for R fpl.
So out of these 27 suspected rccs, only,
or 10 were benign.
And they found out,
because they, these bi these tumors were all biopsied.
And when you look at the final diagnosis, then you can see
that NG lipoma was the diagnosis in four out of the 10.
And the complicated and hyperdense cyst were five,
and there was one focal bacterial pyelonephritis.
So what is the role then of ultrasound
and especially of contrast agent in a ML?
So if a ML is proven by CT and
or MRI, size and vasculature matter
and define the risk of bleeding,
because the risk of bleeding is the challenge
to find out who is at risk, please have in mind that 5%
of AMLs, or in 5% of AMLs imaging fails to prove intralesional fat.
Now this is from a study from Yama Cardo in 2002 published, and they correlated a ML
and the risk of rupture.
And you can see on the left side the size
of the intra lesional aneurysms
to the likelihood of rap of rapture.
And on the right side, the tumor size
and the aneurysm size were correlated to each other.
And of course, with the rising size of the tumors,
the aneurysms also get bigger.
So this is also from the publication of the same group from YA Mecado, showing
huge aneurysms in AMLs by angiography.
Now this is a hyperreal tumor measuring seven
centimeter in size.
The a ML was proven by CT
and described as hyper a ML.
You can see the lower pole of the left kidney on the left
and also on the right side.
And now let's look at the contrast study.
And in the contrast study,
you can see the intralesional artery
branching into at least three aneurysms
that you can see quite nicely on this left image here.
And on the right side we
did a accumulation mode,
and the accumulation mode shows quite nicely the vasculature and the streaming blood into this aneurysm.

Cystic Lesions

Okay, cystic lesions.
Now c is used as the Bosnia classifications
that is well known in the other imaging modalities like CT and MRI.
And this is what you can see on
a gray scale image.
So this looks like a simple cyst with a C five one probe.
But if you use a high frequency probe,
as you can see it here on the right side,
you can see some internal echoes within the cyst.
So this is definitely not a simple cyst anymore.
So then we injected contrast and injecting contrast.
You can see this was a renal cell carcinoma
with huge amounts of necrotic areas,
and that was confirmed of course by surgery.
Now on the next image, you can see a patient,
41 years old,
and she underwent several CT and MRI studies,
but the images
and the studies could not really confirm at cyst
and could also not state that this is a malignant tumor.
They were not conclusively studies.
So this patient was sent to our lab
to perform a SEAL study and just see what is happening.
You can see the tumor quite nicely
and it's taking up contrast very, very quickly.
And it turned out to be a very small
nine millimeter RSCC of the left kidney.
I, This is a
cystic tumor within its cyst.
This is the grayscale appearance on the left side.
And on the right side you can see the 3D image
of this tiny cyst
that has multiple scepter in it.
And we performed a contrast study.
You can see on the left side, shining
through the cyst, the tumor itself.
Now the aorta is filling, you can see the left renal artery
enhancing and the vein,
and now you can see the enhancement of the tumor,
and you can see some cystic parts within the tumor,
but you can also see a lot of vasculature in these thickened receptor.
And this is a second injection.
And you can see the renal artery, the vein,
and the small
arteries that are filling the lesion completely.
So this was a cystic RCC as well.
This is a patient who went to the urologist
because of some prostate problems.
And the urologist did a also a study on the renal
and found out that there was a big tumor
that was highly suspicious for an RCC.
So the patient was sent to ct
and CT says, no, it's a hemorrhage cyst.
So the urologist wondered why he was so wrong
with his diagnosis, but accepted the diagnosis.
And during the following two years,
the urologist sent him each half year to the CT
to confirm the diagnosis of a hemorrhage cyst, which the
radiologist did.
But then the urologist sent this patient
to the next hospital and they looked at all the CT studies
and said, well, this is hemorrhage cyst,
but in order to make it clear, we will puncture this cyst or this hemorrhage cyst.
And indeed what they found out by puncturing this lesion was they found blood,
old blood in this lesion.
Half a year later, the patient was sent to this is the CT study, and half a year later, the patient was sent to us.
And this is what we found out.
We found out that of course there was a hemorrhage,
but you can see on the left side of the sick,
complicated cyst, solid and viable tissue.
And this was an RCC, so that was bleeding complication
of this RCC
and was immediately under the patient underwent immediately, on the next week, surgery
and the diagnosis of an RCC was confirmed.
This is another patient, 30-year-old
and in incidental finding on the
left kidney upper pole.
And when you inject the contrast,
and you can see in contrast to the patient
that we previously saw no enhancement within this cyst.
So why is it so echogenic the cyst?
And the answer is the patient had a severe accident,
10 years ago,
and with the some broken ribs,
what you also can see on this image is a glare artifact.
So this is an artifact due to the superimposed spleen.
So that gives, this is artificial.
These are, this is not a vascular rise.
This is not vascularized tumor.
This is a patient who was sent to our lab from the radiologist who concluded from his t study
that this is an acute renal hemorrhage.
And we were looking at this left kidney
and could hardly see the left kidney in its normal shape.
But when you look very carefully on the left image,
then you can see that around the renal there is a apo rim.
And when we perform the
ultrasound contrast study, then you can see
that there are two renal arteries.
And then you can see quite nicely that we have a
rather normal vasculature of the left kidney,
and you have an enhancement of the por margin that is
around the kidney.
And this is a typical finding for non-Hodgkin lymphomas.
So this patient did not undergo surgery,
but biopsy and biopsy confirmed the diagnosis
of a non-Hodgkin lymphoma.
Okay, now this is here the image after one minute.
Then you can see that the apor margin around the kidney is now washed out.
This is a 70-year-old boy who had a skateboard accident heir.
This is the gray scale image. This was done.
The very first study was a CT study,
and the follow up was being performed in our
lap with the contrast.
And here you can see the appearance of the
laceration of the left kidney.
Here you can see the perfusion defect.
What you can also do is to, for, especially
for controlled studies, you can do it in 3D.
So this is during the arterial phase,
the 3D study of the left kidney.
I can see quite nicely the defect in the middle
of the kidney and how close this laceration was
to the major renal vessels.

Infectious Diseases: Pyelonephritis

Pyelonephritis pathophysiology
and imaging, you have to know something about that.
Toxins from CIA choli, which is the most common cause
for lon nephritis, induc a reduction of the muscle trauma
of the ureter, thus favoring the ascension of bacteria
to the renal pelvis and the bacteria will cause,
and the infection will cause a thickening of the wall
of the collecting system.
And a segmental or global vasoconstriction
and peri focal hyper, hyper vascularization abscess
and progressive destruction may occur without treatment
or with an unsuccessful treatment.
So pyelonephritis is looked upon as a clinical diagnosis,
but persisting fever
or pain over more than 72 hours are indication indications
for imaging procedures in order
to find out the underlying cause
complications of the disease.
So this is a patient with fever and persisting flank pain.
You can see on the left image some renal sweating.
And on the right you see a thickened pelvic
and ureter wall.
And this is the segmental hypo
vascularization that you can see.
When you inject the contrast.
You can see on the right side the still image
that is taken from the loop on the left side,
and you can see a rather clear hypovascular segment on the lower third of the right kidney.
Another patient, when you look at she had also pyelonephritis existing fever,
was the indication for this study.
And you can see the right renal that looks very normal,
but when you look very carefully at the lower pole, just
below the lower pole, you can see a little amount
of free fluid.
And then we added contrast.
And as a surprise for us, we saw some tiny
cystic looking areas in the upper pole of the right kidney.
So this is in February
and on the control four weeks later.
So they discontinued the antibiotic therapy,
they changed the antibiotic therapy,
and she was then dismissed from hospital.
And four weeks later she came back to us
for the follow-up examination.
And you can see now that all these cystic areas in the upper
pole of the right kidney have disappeared.
So no more pathological findings in BM mode and in cs.
And this is another patient severely ill,
he's suffering under diabetes, renal failure.
He had sepsis loss of weight, and this is the left kidney.
And you can see also renal sweating.
You can see on gray scale a thickening of the renal pelvis and the ureter wall.
And when we now look at contrast,
and you can see of course that we have a hyper vascularization around this abscess at the lower pole.
And on the next image, you can see what we did.
We punctured this abscess in order to have a diagnosis.
Which of the bacteria is playing a role here?
This is the gray scale image, again,
with a high frequency probe.
What we are doing now when we, when the needle is
inside the abscess
and we give contrast agent within the abscess,
so then you can see the filling of the abscess.
But surprisingly, you do not only see the abscess,
but you can see a narrow of bridge going into the renal pelvis.
So now the renal pelvis can be seen
and when you wait a little bit
and inject another portion of Contrast agent, then you can see you have a complete filling
of the renal pelvis that is enlarged.
So the patient got a
Catheter in the right renal pelvis.
The antibiotic therapy was intensified.
And then you can see half a yield or no.
Three months later you can see the result, the catheter in the left pelvis was withdrawn, was removed.
And you can see now the thickened ureter wall.
That was very impressive for us.
And we now looked with Cal Doppler and with color doppler,
you can see some that is very nice.
That may be the explanation for also one argument for why this infection took place.
You see the blue color within the lumen of the ureter,
and that is indicating a wrong flow direction.
So there's probably A-V-U-R-A vascular reflux,
and you can see that the wall
of the ureter is hyper vascularized.
So when we add contrast at this stadium,
then you can see that the wall is hyper vascularized.
And the upper third you can see the draining vein
of the uretal wall.

Indications for Contrast Enhanced Ultrasound in Renal Diseases

Okay, so renal tumors and inflammatory diseases.
What are the serious indications that we sees pseudo tumors?
Yes, if you are in doubt
and if color dolin does not help,
pseudo tumors are an indication
for administering a contrast agent tumor detection.
That is seldom, we don't use that on a regular basis only
for certain questions.
Trauma, yes, mostly in the follow up
or in blunt trauma without hematuria to exclude a damage to the renal parenchyma, cystic tumors
or complicated cyst.
Yes, and this is definitely the number one indication
for using contrast agents solid tumors, not in general,
because they're pointed out that contrast agent is not
that helpful in differentiating tumors,
different tumors from each others
inflammatory tumors in titis, yes, in certain cases,
as I just showed the Hodgkin lymphomas, yes,
because Hodgkin lymphomas mostly regard the vasculature
of the renals.
So they, they are, they're still preserved
and you can see the major vessels running through the tumor.
So by this you can differentiate the no Hodgkin lymphomas from solid tumors.
Tumors that are difficult
to differentiate from neighboring organs like adrenals,
pancreatic tumors of the tail, retro panal masses sarcoma.
Yes, contrast agent may help in these cases.
So thank you very much for your attention.