24 Q&A with the Faculty

Question on Benign Lymph Nodes on Diffusion Imaging

If you have questions, please come to the microphone.

This is a question for Dr. Rosenkranz. The case that you showed that on diffusion the lymph nodes were bright, but turned out to be not cancer. This is because they are reactive lymph nodes. Or is there any ADC number you can orient yourself and say this is abnormal?

Repeat the question.

The question is asking about benign lymph nodes that had an increased signal on high b value images. That's very common, common to be expected. Basically, we see almost ubiquitously some mild increased signal on high b value images. So that wouldn't really even concern me in the least to see that, and that was commented on in the recent radiology paper that I was citing in the talk. There they described looking for nodes that really had what they described as very high signal compared to other lymph nodes and correlating it with the standard morphologic features on t2 weighted images, such the round or cyclical shape and presence of the fatty hilum, the node margins.

I find that the high b value images on diffusion useful for detection, for perceiving to pick up nodes. It can be tricky on t2 weighted images versus a flow void from a vessel or if it's just small, or if there's some motion or various reasons. And sometimes you can appreciate on the diffusion and go back and correlate it with the other sequences. But I wouldn't just routinely just take it as showing high signals on diffusion as a marker of suspicion for being a metastatic node. That's very common.

This is an important issue because the lymph nodes are important when you're staging, and I'm curious to see how other people are doing with this. Because in that paper, by the way, they did high resolution images and in reality they didn't do very well with or without diffusion, even though the paper was about diffusion. So I'm curious, does anybody think we're doing a good job with lymph nodes? And is anybody really leaning on anything other than the limited size criteria that we have been using in CT for all these years?

I'm seeing faces.

There are a few things that are going on. One, conventionally using the size criteria, we're not doing well, so we have to do something else. First of all, a number of pet agents that are coming out that I think are gonna do better. And also, we are looking at iron oxide with ferumoxytol, which is an FDA approved agent, not as sensitive as Combidex, the agent that was reported on about 10 years ago. But we're getting pretty good results. We've done about 20 patients. So that's a possibility for staging.

And I will say also that there's data out of Johan de Bono and Anwar Padhani's group in London that the use of diffusion weighted imaging, whole body diffusion weighted imaging for not only bone disease, but possibly also for diffusion of lymph nodes could be kind of a one stop shop for prostate cancer staging that is very promising. We've been trying to implement that and it hasn't gone as well as we've done. I think he's doing it at 1.5 T. Yes, because the diffusions are to be problematic in other parts of the body.

But if we can get that to work, it could be a very good technique and could carry it through castrate resistant prostate cancer.

Right. So there is hope, but at least for now, I don't think we're doing a great job with lymph nodes. Any other comments on that?

Question on Routine Use of Diffusion

Can I ask a question? Yeah. So Andrew, when what do you do? Do you do this routinely or do you do this only in a staging situation? And how much do you cover with diffusion?

That's a good question. This is just our diffusion weighted acquisition that we just have in all of our scans through the prostate. Right? That's already. I'm not doing it separate specifically for, and I think to the earlier question, I think if you're routinely gonna be calling suspicious nodes based on just anything you perceive on diffusion, you're gonna be having a lot of false positives.

I do think it's useful to look through that image set for not showing increased signal, but then have to correlate it with the conventional sequences to make a decision whether or not to raise concern. I find I can make maybe a little bit of analogy to the point we made about using the DCE to improve our visualization or just initial detection of lesions within our final scores based largely on the t2 and diffusion, but perhaps our eyes were drawn to it with the DCE. And I think there's kind of an analogy to that here. I think the high b image adjustment is gonna kind of bring our attention to nodes, but I wouldn't just routinely call them based on that alone.

We routinely scan to the aortic bifurcation and we comment on any nodes we see and give sizes of them, and noting that the size criteria we have are very limited. Although we will, if there's something big there, we'll certainly highlight that and make sure they're aware of it.

Just with one minor thing about, just to add to that, the post contrast images, we take them all the way through the retroperitoneum and enhancement of the lymph nodes is also very helpful.

Question on Artifacts from Hip Prosthesis and Metallic Implants

I have two questions. One is, we see susceptibility artifact from the coil itself, but more often we see artifact from the hip replacement. We try to increase bandwidth or, but didn't work very well. So if you have any measures that's sometimes very critical and sometimes after surgery, susceptibility from the clips.

Let me, Claire, you wanna comment on and repeat the question. Yeah. So I think the question is related to what do we do to overcome the artifacts from hip prosthesis and metallic implants? Is that correct? Yes.

Okay. So three Tesla will make all of those worse, there's no doubt. I find that it is rarely enough of an artifact that it goes actually all the way into the prostate. So I don't have any particularly strong mitigating steps that I would recommend. I think your gradient echo images are going to be harder, and they will obviously have a larger artifact. But the t2s and the diffusions seem to work out pretty well. I don't know if anyone else has any particular mitigating steps.

We move the patient. If they have hip prosthesis, we'll generally move those to a 1.5 T scanner, or we'll start them on the three T. And if the artifact is okay, we'll leave them there and if it's bad, we'll reschedule 'em on the 1.5. There's no simple way of dealing with it right now. Any other comments?

The one thing I would add is, I think similar, I've also found that's variable from case to case. Sometimes they have the hip prosthesis diffusion actually is okay, another times it's completely non-diagnostic, and we're barely visualizing the prostate to the hardware. So to relate this to the comments that's come about DCE and whether this is optional, and do we have to routinely use DCE in every case for this situation that the DCE I would say generally comes out more reliable or robust in the relative to diffusion in the saying that when we have had cases where the diffusion has been essentially non-diagnostic, the DCE is still has been reasonable. So I think if in your practice you're not routinely using DCE, that this could be a case to do it, to have it as another parameter available if should the diffusion be distorted.

We tend to observe the prostate Morton sign where the tumor is always on the same side as the hip replacement. So again, opening up the bandwidth, low field strength, 1.5 Tesla, you can try flipping phase and frequency. It's not magic, but sometimes you get that one little extra area in the prostate that you can see. And it's usually just the EPI DWI that's affected. DCE is robust.

Question on Post-Prostatectomy Imaging

The next one is about after prostatectomy. Do you use like a pharmacokinetic model in every case? Versus just lava sequence?

We use a threshold. Like a PSA one, and then if it is below, then we use lip regular lava versus if it's higher. Anybody want to rephrase the question? Yeah.

So the question is in the case of recurrent disease, do you prefer to use some kind of pharmacokinetic modeling system or simply the raw images as you refer to as lava, but whatever generic term you care to use for it?

So we tend to use just the raw images and look for the dash of enhancement, that it can be very very small. And I wouldn't limit it to patients with PSAs of one or greater. Because we've had cases of less than one down to 0.3 or 0.4. Very remarkable that now these are very difficult to interpret, and you really have to have good technique. The enhancement is not light bulb bright, it's subtle. The anatomy is distorted, it's difficult, but nonetheless, you can pick up early lesions, and I believe much more with much more sensitivity than any of the nuclear scans like FCH or FAVEC or others that have been introduced to address this problem. So I'm actually optimistic about it, but we use a simple technique. I don't we don't use a complicated PK model. It doesn't necessarily improve things. Of course, there's no harm in doing it. So it comes free with the software, you can look at it, but it usually doesn't help.

I think what we use, and they're not widely available, but they're coming more widely available, techniques where you can do the dynamic contrast and hand scan with very high temporal resolution and spatial resolution. I think this is a really good place for it. Because you need you need both to find these recurrences. And again these techniques are, not everybody doesn't have 'em yet, but you will if you have a sort of up-to-date scanner.

Question on Biopsy Recommendations Based on PI-RADS

This is a question regarding biopsy recommendations based on the PI-RADS. And it's something that I'm not sure I heard Dr. Ani say correctly or not, but I think she said PI-RADS three, four or five, she would recommend biopsy. And is that what the entire panel also sort of uses? I'd like a sort of guideline.

I think we're probably having a little debate on the threes. The question is regarding the recommendations for biopsy based on pi rads overall assessments. Is it including three? We all agree it's four and five? I think there probably is some debate about threes, and there are different kinds of threes to be honest. But we do use three. How about the rest of you?

So you we would usually biopsy a three. I mean, we're usually biopsying a three, but I think there's some degree of individualizing it. When we've looked back at our outcomes in level three, in patients with a PI-RADS of three, it's the frequency of cancer and of high grade cancer is gonna vary based on the patient's biopsy history. The level of risk is going into the MRI. So it'll be those frequency would be higher in a patient say who's already had a positive biopsy in comparison with somebody who's biopsy naive or is that a negative biopsy? We found in many who already had a negative biopsy, the rate of high grade cancer in our level three lesions is actually very low. So the decisions can be tailored based on the patient's risk profile. But with all that in mind, for the most part, we're biopsying PI-RADS three.

We do basically the same thing. If it's comes from a urologist, it probably goes to biopsy. If it comes from a medical oncologist, a radiation oncologist, they'll often just observe.

So what I'd say is these are generally decisions that are made between the patient, the doctor who sent the patient to us and the patient. Because you need to with the threes, you really need to have the entire understanding of the history and also what the patient's anxiety level is and a lot of other factors. So we refrain from making recommendations, we just tell 'em, it's a RADS three, this means it's equivocal. It could be clinically significant cancer, it may not be, some of these patients are they're gonna wanna do a biopsy on, and others they may elect to just follow them or take some other approach.

Question on Patients on Androgen Deprivation Therapy

Thank you. So we had a couple patients that came for a staging MRI, then prior to getting the MRI, but they were placed on androgen deprivation therapy with the neoadjuvant Lupron. And we've noticed that the appearance of the prostate was heterogeneous and on the dynamic contrast imaging, the hypervascular area that you would expect to see, looking at the pathology that we got for the biopsy result, we couldn't find the lesion very well on any of the sequences. It was just small heterogeneous and so forth. And obviously we put a caveat that the sensitivity was decreased because of the Lupron. And what do you do in that kind of scenario? What do you tell the clinician? Is there something parameter or recommendation you tell the urologist perhaps that you get the staging MRI prior to the Lupron? Just wanna see what your expertise, Dan, you wanna take a shot at this? Repeat the question.

Sure. So the question is, for patients on androgen deprivation therapy, how do you compensate for the changes that occur in the prostate?

As we've mentioned earlier in the seminar, it's really important that you as the reader know whether or not the patient's had any prior treatment. This includes radiation, but also hormone therapy. And this can even include things like treatment for BPH with finasteride. We'll often see a decrease in the overall t2, so a shortening of the t2. And often there's a decrease in the DCE generally. And in these cases, you're looking more for asymmetry. And for things that are subtle, the DCE will also change, but you'll often still preserve the focal abnormality. It may not be as striking. But again, like with any treated patient, DCE is an important component of the evaluation.

Anybody else have anything to add to that? Totally.

Question on Why Multiparametric MRI Isn't Standard of Care Yet

I have two questions. With all this new data that you guys have presented yesterday and today, why isn't this the standard of care compared to what we're doing today with the transrectal biopsies and the standard PSA? And it's like similar question is, are our urology colleagues adopting these criteria, or are you guys talking to them about maybe working together? Because in the hospital, we work, there's still basically routine transrectal biopsies, that's what they do. And then there's really no adaptation of all these, there's a lot of compelling evidence here, right? So I don't understand why.

Let me try to, I'll start answering and then everybody else can give their view on it. And the question is, why isn't this standard of care? And what I'd say is that, it's still fairly early in the game, in the sense that it's not widely available, just kind of targeted MR ultrasound fusion biopsies or MR targeted biopsies just not available everywhere. I think that there's been an evolution that's occurred in the urology community, and there's still a lot of questions about this. And remember, there's a long history with doing things a different way. Things don't change overnight. Not everybody is as amenable to change as other people. And frankly, this is not perfect. But I think what we have seen unequivocally is that the tide has turned that, as opposed to several years ago where there was just incredible resistance to this kind of approach amongst the urology community and radiologists, quite frankly, that now this is being embraced. And so there's a reasonable chance that it will become standard of care and probably at our places it already is. But these things take time.

You wanna comment? Yeah, no, it's absolutely right. And this is a tidal wave of change and it's been coming for a long time and the data's been building, and I think we're there now. The editorial that was cited by Jeff, I believe it was on the first day to MRI guided biopsies targeted or not, the Lenny Marks versus Peter Scardino. One is a very good description of why, and if you read Scardino's description as to why it hasn't become accepted, the first one is really the standardization of the MRI technique itself and our job as interpreting. And that's why PI-RADS is so incredibly important that our radiology community is now coming together around standard definitions and standard lexicon standardization as we've been hearing now obviously a lot for the last two days. And that's an incredibly important step because I used to, I've been speaking on this topic for many years, and much of the criticism I used to receive was that, my doctors can't do this. I can't do this at my MRI center. They don't do prostate MRI here. And we've had this for years. And now finally, I think people in all of the radiology communities and all of the departments across the country are realizing that they have to provide this service in one way or another. And that's why this educational piece that we're really on the very steep part of the learning curve for general radiology throughout the entire United States. But it's definitely happening very fast.

The difficulty I think in a lot of the urology practices is this is an expensive purchase. It's an expensive set of, it's an investment. These fusion systems cost upwards of a quarter to almost a half a million dollars in many centers. Because you have to buy new ultrasound systems, you have to buy the IT pieces and getting everything on board is not a simple step. And as you compare that to what is still a five minute procedure in a doctor's office, and it would be interesting if some of the urologists wanted to jump in in some of this discussion. Because I think that's one of the barriers. There's no barrier as far as I know of with reimbursement and payment and all of those things that are typically the barriers for new technology and new things moving out. But those are the big issues as I see it.

But if you don't mind the, the MRI itself is available and it's not being used currently to its limit, to just on the negative biopsies, for example, or some of the other indications. It's not just the fusion. So that adaptation of just the MRI as a follow up on the negative biopsy or even on the score. It's multifactorial issue.

There's a lot of issues, but it's not unlike breast MRI when we started doing breast MRI years ago, it took a while for it to catch on in part because there just wasn't solid data. It took time, but also the capability of biopsying under MRI guidance wasn't available. And so just finding things and without having a capability of doing directed biopsies really isn't doing anybody a whole lot of good.

Any other comments about this before we go into this question? Well, one thing I often hear is the pushback that there has been no large multi-institutional trial with controls that show a benefit, especially a cost benefit analysis. And so some of these trials are emerging from around the world, but to my knowledge, not in the United States. And it is something we need to do as a community to.

Yeah, and again, this is a chicken and egg thing. You can't do a multi-institutional trials unless everybody's interpreting them the same way. And you have standardized criteria. So again, this is why this PI-RADS thing is so important, even though it's imperfect, if we all start using it, we can actually start pooling our data, comparing our data and doing multi-institutional trials, which presumably will validate beyond any question that this approach is better than what we've been doing in the past.

I would caution that I think multi-institutional trials on the biopsy themselves is going to be very challenging. Yeah. We're all using different approaches. We do it in different ways, but the meta-analysis and the Moore et al paper is a nice one. The results are very similar. Everybody's pretty much getting the same, approximately 50, 60% hit rates and showing much more clinically significant disease and higher volumes and all of those good data that we've seen. So I'm not sure that we're ever gonna do a multicenter prospective trial comparing biopsy approaches, but it's clear from the data that it's a definite advantage. And Pete is absolutely right. The English and the Europeans have done the cost benefit analysis and looked at that in NICE decision systems. I showed quickly one of those yesterday. And the data's pretty compelling on the costs. And the UK NHS is really adopting this pretty rapidly, and they're very cost conscious, and we do need a similar study with US dollars replacing euros and pound sterling, but it will be done. And I think that will hold up because there's less cores the less all of the pathology costs. You gotta factor in the whole thing. They're going down considerably with this approach.

And by the way, the cost of prostate cancer, of dealing with prostate cancer in this country are so enormous that, if with prostate MR at first look, you go, this is a really expensive test. Are you really gonna do this annually? And are you really gonna do this on people before you do a know that they have prostate cancer? And the answer is yes, it probably, although we don't have the data here in the states, it probably in the end will actually end up saving a lot of money and result in better care for the patients.

Written Questions from Webinar Attendees

Let me just, there's a bunch of questions that we've received in written form from I think people following this on the webinar. So let me just let's see if we can get through these quickly. So let's see if keep the answers the short if possible. Let's see, Claire, is there a minimum PSA value required before doing an MRI to look for recurrence? Recurrence?

So recurrence after prostate cancer surgery, there's no minimum, it should be zero. So if there's anything above zero, as we already discussed in the post-radiation patient, you use the Phoenix criteria, which is nadir plus two.

PI-RADS and Extracapsular Extension

Let's see, for Andrew, PI-RADS include smaller lesions with extracapsular extension. I'm gonna see if you follow this, how definite does the extension need to be in over how long a distance? And how often do you change an assessment from a PI-RADS four, meaning a 1.5 cm or smaller lesion, to a five based on extracapsular extension? Can you answer that in three words or less? Yes. No.

So it sounds like the question is asking what degree of extracapsular extension we need to appreciate to bump a lesion from a four to a five if I'm. I would have a hard time answering, so that's listed as one of the criteria for a five. I don't just to my knowledge, there's no explicit measurement in terms of EPE or amongst the various findings we can use to call explicit finding which ones to use to make that change from four to five. So I just think it's still kinda left in our own hands as the interpreting radiologist. I don't think I could give a hard and fast rule that would apply case to case.

Yeah, I mean, there you know, the number popularly quoted in the literature of that, if there's that greater than one centimeter of contact between the tumor and the capsule or the pseudocapsule, the outside of the prostate, then that suggests extracapsular extension. But I think it's a probably a pretty weak sign and I would not depend on.

No, the in terms of the actual millimeters of contact between the lesion and the capsule to EPE, if you look across literature, there are studies suggesting 10 millimeters, 12 millimeters, 15 millimeters, none of it seems to really be based on good data. So I don't know if that's really gonna help too much. Okay. And we're still kinda left on our own.

Let me go on to Peter. Go ahead. Just make a quick comment on that, that you know, I'm often I find myself often caught between the radiation oncologists and the urologist for where the patient's gonna go. And this extracapsular extension becomes sort of the bone of contention between the two. And I hate to see based on what we all know about how we're not quite clear about EPE, I hate to see a decision on treatment made from this finding. Yeah. So I tend to downplay it for that reason.

Yeah, I we handle it the same way. And the notion that we're gonna see microscopic extension and even what that means in terms of treatment is so contentious that I just don't go there. And as I mentioned, if I see gross extracapsular extension, I'm really pretty confident with these subtle things. I think sometimes you're right and sometimes you're wrong.

Daniel, you wanna comment? That's basically what we do. If we see the obvious irregularity of the capsule, even if it's small, we'll describe it as minimal. But if we're confident, we'll bump it up to a five.

Systematic vs. Targeted Biopsies

Okay. We had another question out there. It's the second question that I had. You mentioned earlier, Jeff, that you do systematic biopsies at the same time you do the targeted biopsy. And I don't know if I heard you correctly, you said sometimes you find more significant lesions with the systematic part of the biopsy, not the targeted. And I also you know, throughout the lecture, kind of heard from multiple speakers that sometimes you don't find the lesions well on MRI. Is that like a because it's hard to understand how you can see the lesions so well, and you target it, and then there's something else somewhere that you don't see at all. So the question is that is even more significant, right?

So the question is about do we find everything with MRI every clinically significant cancer? And there are times when you find cancer, when at either a radical prostatectomy or a systematic biopsy, do you find clinically significant cancers missed on MRI? And the answer is yes. And as Peter mentioned, most of the cancers that we miss on MRI found on systematic transrectal ultrasound guided biopsy are clinically insignificant. But absolutely, there are ones that we miss. It's not a hundred percent maybe. And over time we'll probably get better, we'll figure out how to do things better, but absolutely we're missing clinically significant cancers, no question about it.

Any other comments about that? The UCL paper show that nicely, I mean, there's obviously a significant, depending on how you define clinical significance, as you get more and more the there's you know, somewhere between what is it, 40 to 5% that are just missed? I mean, so it ranges really depending on what criteria you're applying for clinically significant.

Yeah. Remember I showed you a slide illustrate this. It's not that MRI is perfect. It's not that PI-RADS is perfect, it's that we're raising the bar. It's better and reproducibly better. And across many places and many countries now, it's better than just doing a systematic biopsy. That's really where we're at right now.

I think there's also two issues playing into this here, with the decision to do systematic sampling at the time of the fusion biopsy, there's this recognition that of false negative rate in MRI, which we're still kind of learning and getting our hands on, in addition to a fraction of registration error. I mean, we've had what we'll see from time to time cases where the fusion core is negative, but the nearby or adjacent systematic core has tumor. And then the fusion core what didn't have inflammation, it was just normal tissue. And then the so presumably it was just some misregistration. So we're still stuck with dealing with that. And it I think leaves us with the issue of until the fusion registrations, I think it still needs, I think these algorithms that the vendors are offering still need continued optimization. And in the meantime, I think we're we still sometimes will do the systematic sampling, not just because of the false negative MRI, but also to deal with registration issues.

Spatial Distortion in DCE Maps for Fusion Biopsy

Right? So in fact, there's another question here. Maybe Dan, you can take this one for accurate targeting of MR ultrasound fusion biopsy, how do you compensate for spatial distortion in a DCE maps?

So that's an important question. When I was processing the case, there was one case where I propagated the region of interest that I drew on the t2. In general, that is not our practice. We draw a separate region of interest for DCE and ADC because of not only the geometric distortion from EPI, but translation of the patient from one acquisition to the other. So I have some physicists working on a way to simultaneously acquire DWI and t2, which will obviate that a little bit. But there are techniques that are upcoming where not only does the software automatically register the capsule of the prostate on t2, but on the other pulse sequences to adjust for the geometric distortion and translation. Until that time, I think it's important that you if you're going to try to propagate the ROI, that you make certain that it looks like it's in the right place, and if it's not, you should redraw it. And the newer software will actually allow you to label regions of interest as the same lesion on different pulse sequences.

Payment and Ordering for MRI

Regarding payment. What would be your recommendation, how the urologist should order it, and how do you bill for each one for a screening and for staging? How should it be done that you get paid?

Okay. So a question is how should this be ordered and by the urologist? And probably you should avoid the word screening since CMS doesn't like the word screening unless it's for breast cancer as a rule. But so how are you handling it? There is an ICD nine code for elevated PSA, which is a presumptive diagnosis of prostate cancer. Obviously it's not really because it can be prostatitis or many other things, in general that does allow for reimbursement for Medicare and a number of private insurers. If there is a known positive biopsy, then you're sort of golden. Generally the coding term is MR pelvis without and with contrast, you can also separately add the billing code for endorectal coil, bill separately, the glucagon, if you use that. And if we do MR targeted biopsy, we add on the 3D processing code.

Do you get paid? I know you bill for the endorectal coil. Do you get paid for it? Who knows? Probably not. Maybe.

Yeah. You can bill for anything, but that doesn't mean you're gonna get paid for it. But I'd say my own experience is it really hasn't been a problem. If there's a legitimate reason, but I would avoid the word screening. That's like a red flag.

Yeah, you need to use high risk or because we're not screening something. Yeah, you're not screening and I wouldn't use that at all. And it has to be based on a risk assessment. So high risk for prostate cancer or family history, people put a lot of these different things together.

PI-RADS Version 2 and Practice Outside Urban Areas

Alright, another question, written question here. Let's see. We run a program, we've run a program for over a year with our urologists support and satisfaction. This will not change anytime soon. Will your PI-RADS v2 address this type of practice? If this can be done on any patient outside of an urban area who will not have access.

I'm not sure what the question is, but PI-RADS version two again, is meant to be simple and meant to be used not just by folks like here at the on the panel who are on academic medical centers and big urban areas meant to be used by everybody. And hopefully it will be.

MR-Ultrasound Biopsy Systems Comparison

Or the various mr ultrasound biopsy systems on the market equivalent, or is one technology looking better than the other?

So I think Daniel, you would sort of addressed this, the pros and cons of each of them in your talk. Yeah, I'm lucky that my urologists are very finicky and temperamental. So we've actually evaluated the Qualis system, Eurostation, and we have both AV from InVivo and Artemis from Eigen. What I've found is, as a radiologist, I don't get to choose. The urologist tells me, this is what we bought and this is what you're using. That being said, it really there are advantages to all of the systems. The articulated arm can be a little cumbersome, but it also stabilizes the probe. So the urologists that have gotten used to it, really like that, the ones that haven't think is really cumbersome and like the electromagnetic tracking, which is a little easier at the outset. Our crosstown rivals at USC use Qualis, and that has the advantage that you don't really have to buy any extra hardware, but you have to get used to the step and shoot method where you basically stop moving, tap a foot pedal and it tells you where the target is relative to where you're pointing. And then if you're going to move the probe at all, you lose that so you don't have real time tracking. So it I don't know that there's one technology that definitely wins out. It's sort of user preference, but they all have their respective advantages.

And what I'd say is and I agree with you, the you know, what I've seen is the system that's being used, this is not the workstation that the radiologist uses, but the MR fusion ultrasound fusion system that is being used, generally the person who's doing the biopsy is gonna make the decision, and not in most places, not all. That's been the urologist. And the other thing I wanna say is we have to be a little careful here. We can't we don't wanna show any bias or favoritism to one vendor or another. So we have to be a little circumspect about how we answer these kinds of questions.

I mean, I would just add to that, that so for the various vendor systems, there is there are separate studies for each of these systems supporting their value compared to just a cognitive biopsy approach. There's no study that I'm aware of comparing any of these different fusion approaches. Say the robotic arm versus electromagnetic navigation compare head-to-head one versus the other. So that data doesn't exist that I am aware of. I mean, in so I mean, it's as it's been said, it'll be the urologist's choice and you'll find some urologists be very bullish about their own choice and then give 1,001 reasons why they feel their system is the preferred one, or the approach they use is works better. But it's really largely you can hear some very compelling arguments, but it's not necessarily data based. And I think at this point, it's just what I think is working well in each operator's hands. I think that's actually gonna be important area for investigation to actually compare so actually quite different algorithms for achieving the fusion. Actually try to see if we can sort out which is the which might actually be the optimal method.

Claire, did you just wanna say something? Well, there's a great number of people very interested in the registration tools that are out there in the various algorithms. And the MICCAI community and the computer scientists of this world have a lot of open source and registration challenges that go on comparing them. And it's unfortunate because we really have two worlds. We have our sort of research investigative folks who are doing this in a sort of an open source way. And then unfortunately it was classic when you move into the commercial product, things become a little bit more proprietary and a little bit more black box, and you don't really know which algorithms are actually being used. And I think we at this early stage of penetration, you're not gonna know that for a while. But as the devices become more and more used, we will get to a point where we will be able to compare across device and device. But it's an incredibly important topic and I don't think we wanna lose sight of that yet. But you know, if you want to learn more about registration, I would talk to computer scientists and they will explain the rigid versus the non-rigid, the finite elements. There's many many different types. And then of course, a lot of it is in the perception of where that capsule is and who the operator is that's actually drawing that to provide the raw data and the input in the first place.

Yeah, so I think that's an important point. There is now because the technique has been validated and because the tide has been turned and there's so much interest in it, there are now a lot of resources and a lot of really smart people who are working on refining these techniques. And I think you're going to see a lot of progress and improvements over the next couple of years. And which again emphasizes that although this has been in development for a long time, we're really just really at the beginning, it's still very much in its infancy and is gonna get a lot better over time.