I'll take any questions if you have for the panelists. Otherwise, we'll conclude the session. Thank you so much. Oh, Babu. You talked a little bit about, you mentioned imaging, right? But I didn't see you being really focused on specific imaging pathways or specific imaging protocols as predictors, right? You said MR and CT is a little bit in the back end. Correct. Well, for some reason, but. So what I showed versus what I currently do is everybody comes in with a doctor. That's usually, you look at that by yourself. And then the doctor is a good screening tool that's a great follow-up tool. A lot of vascular surgeons just do a doctor and then take them straight to the operating room. We don't do that. We either get a platypomphology, MRA, head and neck, look at the arch, look at intracranial, look at tandem lesions. You'll find all sorts of things with these studies. And then look at the plaque to see if there's a hemorrhage. Also, if they're asymptomatic, get the TCDs to hear silent chirps. And a perfusion study to see if it's a non-isolated circulation. I mean, there's not a whole lot of data, but CREST needs to, when you're specifically looking at hemodynamic flow, looking at NOVA to really see if they can start looking at factors to help you predict how the risk would address the disease. I see you getting this thing on the head there, right? Everybody has some type of choice. And so at your facility, you may not have all the cool stuff that's either from the MRI, to see the plaque morphology, as well as what they have, as well as other hospitals have. So it varies right now with what you feel comfortable using and to help predict. The TCDs are great. I think that if we, the discussion here was meant to be with asymptomatic, but if we could be all day here talking about symptomatic, versus asymptomatic, the plaques are probably going to be very different. But if we were just to do some of the asymptomatic side, if you have a very irregular plaque on any of the sites, whether you did it all the time, or you kind of have to use your clinical judgment at that time, I do also use the TCDs to monitor for micro-embolites. But that aggressive dynamic, I think that that's what's going to be the key for how aggressive you really are with this asymptomatic population. Yeah, I would argue that the term plaque morphology, if you throw it out to 10 different radiologists, they're going to give you 10 different MRI results. Right? Right. And so that to me is, there's some great data on good imaging for plaque morphology in different ways of looking at it. But it would be very interesting to see if there was some way to standardize what plaque morphology imaging means or wants. Now, we're going off a, we don't have that. But it's just new discussion that we're having right now. Hopefully we'll get to it. But frankly, it's not that new, right? I mean, there's discussions in review papers that are damn near eight years old, right? Where that word is, it's back to communication about disease, just like in uricer, you say a red shirt, far lateral, means three different things, three different people. Plaque morphology imaging also means something different to us than it means to reality. It's a key one fact to have to look for blood and then a bold to look for necrotic material. But, you see. No, I mean, this is one of my concerns about PRESS-2. Is it, the idea of the illicit variation, which we talked about yesterday, is just percent sclerosis. So if you're in a syndrome like yours, you participate in PRESS? Yeah, we are. So are you taking your patients in that have a plaque morphology that you're worried about? Do you bring them in the trial or do you treat them outside the trial? I think it's a real risk of selection bias. I think it is, our triage is every asymptomatic patient that can be enrolled in PRESS-2 gets enrolled in PRESS-2 first. If they cannot be enrolled in PRESS-2, then we figure out, then we use our, if they are excluded from the trial, then we use our own discretion to put them in other single arm registries or something. So that's the deal we made with Tom Brock that we will not cause a bias by putting people in PRESS-2 first. And then, if they are excluded, then they have the right to do whatever we think is the right thing to do. Yeah, that's asymptomatic, right? That's the advantage of having asymptomatic. If they become symptomatic after a trial, then they fail. No, what I'm saying is, if there are centers that are evaluating plaque morphology, because as Bob was saying, this has been around for a long time. We're still using the same thing we used at ACAS, which is over 20 years old. If you have centers that are taking the patients that are high risk by plaque morphology, you'd say, well, I can't cure my situation. I don't have echocoids. I feel this patient's high risk for having a stroke. We're gonna treat them outside. So then you're only enrolling the patients that are low risk. You're gonna end up with a negative trial. That's the beauty of the stroke trial that we did. It took care of the echocoids thing. When we randomized people to medical therapy versus thrombectomy, that was hard. This is not really that hard, because I think we wanna get this answer off our backs. And I wish CREST-1 had a medical arm that would have addressed this. Unfortunately, we're back in another long trial. The good thing is CREST-2 has already enrolled 1,000 patients. So it's moving, and usually as the trial gets to a later phase, the recruitment rate goes up. So hopefully it would not take us eight more years to get the data. Question? Well, I have a question and a comment. I would like to hear what you guys have to say. So every time we say symptomatic versus asymptomatic, well, we check for numbness, tingling, and language, and all that. Should we be checking for cognitive decline? As ourselves, the patient are having neuropsychological decline, and they become from the, they jump from the asymptomatic to the symptomatic group. Good. Look, I'm gonna tell you that I wish that we did. I can tell you that I've had patients who, you know, my vascular surgeon said, like, oh, no, I don't wanna take care of them, because they have mild dementia. Come on, man, like, really? But I don't know that we have enough data to support that. Hopefully that branch, right, is that, that's what that's meant to try to prove, that there will be a difference between doing that or not. Should we be doing it now? I guess if you're not on the trial, you can consider it, but it's not technically indicated. If you wanna be strict about your, you know, evidence-based medicine, there's not necessarily the full evidence for it. So, here's the, the clinical space is such that the guidelines currently for asymptomatic based on the ACSD and CAS are only 60% stenosis. We don't treat 60 or even 70%, we enroll them now in PRESS, but if they are excluded from PRESS, we don't treat them until they get to 80% stenosis. So, when we are enrolling a patient who is not, we're treating a patient who is not enrolled in PRESS, too, then, who has high degree of stenosis, we always do a perfusion. Perfusion shows a markedly delayed one hemisphere, that is the guy who's gonna have a problem with cognition. Second, we do an MRI on all these people, pre-screening MRIs, and all their leukoidosis on the side of the stenosis. That's another reason to worry about this person having a cognitive decline related to stenosis. And so, while they're still, by definition, asymptomatic, we treat them a little bit more promptly than a true asymptomatic patient without those problems. But now that you mentioned CT perfusion, I personally do CT perfusion. Should we do more CT perfusions on every, on every single asymptomatic high degree of stenosis? So, so, the way we enroll the patients is we do one study, either an MR or CT. If it's MR, it's MRA and NET with black morphology and perfusion. Or, if we do a CT, CTA and perfusion. CTA and NET and perfusion. This one study is being done one time for each new patient, and then we just follow them and die. So, I mean, I give you big credit, Adnan, for the way we looked at this disease, because unfortunately, just like the aneurysm size, it's not everything. And I think if anyone reads between the lines, I mean, this study, the CREST-2, the two PIs are my colleagues, and if you read between the lines and you see, you know, why was it funded with almost $39 million, I mean, it is, the study is designed to show that we should not be treating those 70%. And it's designed in that way. And that's why I think, you know, it's very important for enrollment in this study to be careful about which patients get enrolled, which patients do not. And I think we're all curious to see what the results are gonna show, but, I mean, I'm fearful to show that it's gonna be another Sampras or a bypass trial where we funnel all those patients into one basket, and then we show that there is no benefit for this basket. And the eggs in the basket have different colors and have different, so many things. And, you know, I don't know what's gonna show, but I think the way it should be approached, just like it's individualized. We see the cognitive decline, the TCDs and everything, so that's my comment. Thank you. Okay, thank you guys, and we'll see you tomorrow.

imaging

predicting risk

asymptomatic carotid stenosis

plaque morphology

MR scans