Ultrasound Contrast Agents in Prostatic Disease and Recurrences - SD

Introduction

I am Professor Rodolfo Campi from Pavia, Italy.

I've been director of the Institute of Radiology of the University of Pavia since till 2003, and I've been involved in the study of contrast agents in ultrasound since 1991.

And this was the first publication we made in 1994.

With the results of our first studies, I would like to thank Professor Barry Goldberg and Dr. Waldrop and Dr. Fosberg for inviting me here in Atlantic City for this talk.

And then please let me thank even Dr. Francesco Zaia for the huge work he did in these years.

And for Professor Fabrizio Cal, the director of the Institute of the Radiology of the University of Pave for all the advices he gave me.

Ultrasound Contrast Agents in Prostatic Disease and Recurrences

Today we will talk about ultrasound contrast agent in prostatic disease and recurrences.

The first question we put is, why should we use contrast agent and let us explain what happens after prostatectomy after prostatectomy for prosthetic cancer.

Usually PSA level remains the most used study, although Pete Pet with choline and US studies have been proposed, but PET with colline has still high coasts and up to now it has poor results.

While ultrasound studies at baseline with gray scale and power Doppler show poor sensitivity, biopsy under ultrasound guidance is mandatory.

But often it's very difficult to locate the area to be biopsied because there are no visibility.

There is no visibility of the area.

Prosthetic biopsies are highly invasive and difficult to be performed due to the poor evidence of the area of the recurrences.

So we must put the question again.

Why should we use contrast agents?

Because we must remind the limits of sonography, which are represented by weak signals, absorption, attenuation and distortion of the signal, low signal to noise ratio, elevated noise, which becomes higher in the vicinity of larger vessels and poor signal in slow and weak flow.

So why contrast agents?

Because there are some limits of transrectal ultrasound examination after prostatectomy.

The junctional area is very thin and small, and the number of vessels represented in that area is very low, and they have a slow flow.

So the prosthetic cavity is much more difficult to be examined due to the absence of an acoustic window represented by the prostate.

And finally, it is very difficult to see bleeding vessels.

So why contact agents?

Because we have some targets in our clinical study, which can be summarized in possibly reduce the number of biopsies.

And to do this, we want to improve visibility of vascularity of the prosthetic cavity, shown newly formed vessels inside and surrounding the currency, counter the number of vessels which enter in the tumor and evidence the vessel from which they origin perform inflammatory and, and if possible in the future, establish an algorithm for the study of oxygen consumption by the currency.

Study Overview

In our study over 2000 patients, we selected 345 patients, ranged 55 to 86, who underwent prostatectomy after the diagnosis of prosthetic cancer was reached by ultrasound and contra agent.

Among them, we choose a group of 99 for this study with a minimum surveillance of three years when operated.

81 over 99 when in T two, two stage and 18 in T three stage, all were N zero.

None of them had adjuvant therapy.

In all these patients, PSA has been monitored and the pelvic fossa has been studied with transtectal ultrasound at baseline with gray scale and power doppler.

After that, we have injected ultrasound contrast agent searching for local progression of the disease or for local recurrences.

In the years, we have always used the five nine megahertz and five endo cavitary probe.

With these technical data, which are represented here in the years, we have used two different equipments.

One was an A-T-L-H-D-I 5,000 at the second, a Phillips EU 22nd with second harmonic imaging module.

And in the years we have used two different contest agents vis SHU 5 0 8 by sharing Berlin, Germany, and son of UB one by BRCA Milan, Italy.

Images have always been recorded on CD and on videotape.

Parameters Evaluated

For the results, we have taken into consideration the following parameters.

First of all, the present or absence of detectable vessels, then the distribution and morphology of the vessels.

And we know that normal vessels are different from pathological vessels, which usually are ous have an irregular caliper and course, and in them the branches originated 90 degree.

Then we have performed inflammatory and we have studied the resistive index, which have been, has been considered higher or lower than 0.7.

If resistive index is lower than 0.7 and PSA higher than 0.3 nanograms per milliliter biopsy under power doppler guidance and ultrasound contrast, agents of the antic area have been performed.

Results and Examples

The results can be seen in the next images.

For example, in this patient, we had the suspect that there was a recurrence, but without contrast agent and with power doppler there was only one vessel visible in the area.

But after contest agent, many vessels appear and they are much more better visible.

And so we could study them in a better way.

Another example, only one was vessel at the periphery of the lesion.

But after contest agent some other vessels appear.

As you can see here, and in the latest phase, there are many vessels inside the lesion, which give an idea of the contours of the lesion.

This allows us to an easier inflammatory.

Another example, apparently no vessels or a very small and slow flow vessel appears in the first image.

But after the use of contrast agent, a larger vessels appear, which can better seen with color doppler than with fo power doppler in this image.

Another example, some vessels appear few seconds after the injection of contrast agent, but many more vessels appear afterwards.

As you can see in these two images.

And in the third image, the vessels give you a three dimensional idea of the lesion.

And this is very important for the surgeon.

Another example before the injection of contest agent, mainly peripheral vessels and a a intratumoral vessel.

But after the injection of contrast agent, many vessels appear at the periphery and they form a real three dimensional image of the lesion, which is very well visible and can be biopsied very easily.

Another example in which before the injection of contact agent, you can just see only one vessel inside the lesion.

But after the injection, you see the line, the delineation of the complete lesion, which is much more better visible after one minute after the injection.

And after a couple of minutes, you have the exact idea of the three dimensional image of the lesion and what we have seen with power and color doppler can be seen even with with gray scale.

And here you see before the injection of contact agent and after the injection, there is a hyper echogenic area here, which represents the tumor.

Patient Groups Based on Resistive Index

So the basis of the resistive index, the patients were subdivided into two groups.

Group one formed by 51 over 99 patients with resistive index lower than 0.7.

And in this group, six patients with resistive index lower than 0.7 and PSA higher than one nanogram per milliliter had hypo coic areas, which was suspected as recurrences at Basel Gray Scale.

They were confirmed at power doppler.

And after sonographic contest material administration, we saw hypervascular and tortuous vessels with the typical patterns that we described for tumoral vessels.

In 18 of the remaining 45 patients, recurrences were found with a hundred percent of biopsy confirmation.

And the final 27 patients over 51 are disease free and show PSA lower than 0.3 nanogram per milligrams.

Here let us see some examples of patients included in the group one.

So here you see before the injection of contest agent, only one vessel is visible, but many vessels appear some seconds after the injection and after a longer period, large vessels appear and given a exact idea of the dimensions of the lesion, which is better shown after 55 seconds, one and a half minutes after the injection of contrast agent.

Another example with more vessels, few seconds after the injection of contest agent, but larger vessels appear afterwards after one and two minutes.

And these have the typical patterns of pathological vessels as described before.

This was group one, then we have group two in which we have 48 over 99 patients with resistive index higher than 0.7.

In six of these patients we had recurrences, which were already seen as at gray scale.

They were hypoechoic areas confirmed with power doppler before and after sonographic contrast material administration.

In the remaining periods, patients which have been constantly monitored sonography shows that the patients are still disease free.

Some example, this patient had the vessel, which was 0.71, but after the injection of contest agent, we saw more vessels and they have lower resistive index, which means that not all these vessels should be considered pathological vessels like in this patient where we have some vessels showed by the injection of contest agent with a lower resistive index.

Then 0.7, another example, a 5.6 vessel, which after the injection of contrast agent show lot of vessels and all of them have a resistive index lower than 0.7.

Diagnostic Improvements

As we said before, at baseline gray scale ultrasound often fail in showing the lesion.

And in effect in our study, baseline gray scale ultrasound sensitivity and specificity appear poor with poor positive and negative predictive values.

But after the injection of contrast agent and the use of color and power doppler, we observe and improve in sensitivity, specificity, positive predictive value and negative predictive value.

This is just to remind to myself what specificity and sensitivity mean.

The addition of power and color doppler and contest agent adds higher accuracy in detect lo local currency by biopsy, which RAI raise from 71% to 86% in sensitivity while specificity rises from 89 to 99.5% if we compare it to baseline gray scale and to the biopsy performed with that mode.

So why does this happen and why do we use contrast agent?

This is the answer because contrast agent in ultrasound better shows the vascularity of the lesion, making it easier to detect the pathological area and to perform biopsy under ultrasound guidance due to a better imaging of vessels in the tumoral area to the morphological pattern of these vessel and two inflammatory, which is easier to be performed.

So on the basis of our personal experience, we have chosen the resistive index as a very important parameter.

The choice of considering pathologic resistive index under 0.7 was related to the fact that usually resistive index about 0.8 or 0.9 is considered normal and at the, and that in the subcapsular area it reaches 1.0 and we know exactly that resistive index alone is not able, cannot allow us to differentiate between the normal and the pathological and asmo area.

But if we find more vessels all with resistive index higher than 0.7, then together with clinical and laboratory findings, we can say that that population of patients has a lower risk of recurrences.

Conclusion

To conclude in our patients, we had always enhancement of the vasculature of the junctional area in the prosthetic cavity.

In all patients, we have seen morphological vascular differences between normal areas and recurrences.

And thanks to the intravascular residence times of several mins of the currently available sonographic contrast agents, both with doppler and gray scale, we had the time to clearly study the enhancement.

Pathological areas show major enhancement and typical vessels.

So patients with resistive index lower than 0.7 should be monitored for a longer time with frequent examinations to show the earliest signs of currency.

And the use of contest agents highly facilitates.

The diagnosis of recurrent better indicates to the surgeon the site to be biopsied and makes biopsies under ultrasound guidance much easier to be performed.

It allows to reduce their number and to reduce the discomfort for the patient.

What's more important, and we haven't talked about that, is that reducing the number of biopsy that is an important reduction of risks for the patient.

Why this? Because usually working in a blind way, it is necessary to perform 12 to 24 biopsies to reach the diagnosis.

And due to the thinness of junctional area, there are many possible risks.

Hemorrhage, ureter, action infections, vesical perforation VA episodes among all.

Another advantage in our Italian sanitary reality is that usually after the diagnosis of recurrent has been made by the radiologist with the use of contrast agent, the patient is sent back to the urologist who will ask a biopsy which can be performed again by the radiologist or by himself.

In this case, the patient undergoes two different sessions, while if there are geologist himself performs biopsy under ultrasound guidance.

After the diagnosis, the patient undergoes only to one session for diagnosing and biopsy procedure.

And this is the last example I want to show you, in which there is a very poor vascularity before the injection of contact agent.

But after the injection, you may see more vessels visible and this allows you a better diagnosis and an easier flow, which allows to be performed even in areas which apparently at the beginning seemed normal.

So what can we do about the use of conscious agents in recurrences after prostatectomy that clear evidence is shown that the vascular supply to malignant tissue is completely different from the vascularization of normal prosthetic tissue.

And this is valid both for primary tumors and for recurrences.

The images obtained with traditional power doppler or gray scale after injection of contest agent are sufficient to allow the diagnosis of recurrences in a very high number of cases.

Of course, in the future, the use of contrast agents showing microvasculature the use of intermittent imaging of new modalities or new modules to improve ultrasound contrast agents could be useful to improve the results and to selectively identify the patients with recurrences.