 So you'll have a Q&A session. Anybody in the audience have some burning questions? I have a burning question for Nishant. So actually, I have three questions. Wow, OK. One is simple. One is we keep hearing this PYP scan not being FDA approved, and yet we are using it all the time. It gets covered and blah, blah, blah. What is the disconnect there with that FDA? What's going on out there? That's one. Second, now that you mentioned HTTP, it's fascinating to hear about that one. And you also mentioned the fusion CT imaging. And you also mentioned that the washout is pretty fast. So how quickly do you have to get them to the CT imaging as soon as you're done with the nuclear imaging, right? So the second and the third question is that it could be a $64 million question. I'm just associating, for you to remember, the fee 64 lieu in the way of $64 million question. Is there any specific ethnicity like we have for V121i that's more common in the African-American population? Is there any ethnicity? So those are the three for you, and then we'll go to you after. That's a lot of them. I'll try to take this one at a time. So the reality is that we actually don't understand exactly what we're imaging with the bone scintigraphy studies. There's some suggestion, at least, that there's microcalcification that's associated specifically with TTR as opposed to AL. But the reality is that we actually don't know why these agents. It was sort of a serendipitous finding, and then we sort of ran with it because we have the ability now. There was a Bocari paper that basically showed that you could differentiate between AL and TTR. But we actually don't really understand the mechanism by what it happens. And there's some work being done by Sarah Cuddy and Charmilla Durbal and others to really understand, can we get more AL or TTR-specific agents that bind actually to the fibrils as opposed to, let's say, microcalcification? So that's coming down the pipeline. But that's part of the reason why we don't necessarily have FDA approval for these things. With respect to the genetic variants, it's not just V64, though. So V30M and other variants as well also don't show up on PYP. There are populations. So for example, I was in South Korea a while ago, and V30M is more prevalent there. We don't understand why, but they have to have the same thing that we just discussed in this case in terms of understanding that they may have PYP and HDP imaging that may not show their patients for the disease that they actually have. You mentioned about HDP and PYP and the timing of SPECT and CT. So the reality is that we're doing SPECT CT. So it's the same machine. And in fact, you acquire the CT first, and then you acquire the PYP imaging afterwards. But it's all done in one setting. And it's all done at specific timing. So again, for me, PYP is at about two and a half hours. HDP, I've told my techs no later than two hours, somewhere between one and a half and two hours afterwards. I think that answered everything that you asked. I'll just add to that with regard to the PYP imaging. ASNEC guidelines in 2022 has gotten rid of planar. And it's not just about SPECT. It is about SPECT with CT for formal confirmation. So if your centers aren't doing it with the CT, those are some things I would really advocate for your champion. Because I suspect, Dr. Warner, each of us at this table have seen plenty of false positive PYPs. And these patients think they have a terrible diagnosis and they're getting this very expensive medication. And you can tell them they're actually OK. So you really want to be confident in your diagnosis and use the proper tools. Sam Ibrahim. Thank you, Dr. Vijay. And thank you to all the distinguished speakers. So I just wanted a little bit of clarification, especially with the new guidelines. The clarification is specifically on the role for biopsy. Is there any role now for biopsy, specifically for the diagnosis? I know that the guidelines specifically mentioned that there is a role to rule out, like a false negative. I think one of our speakers is going to be talking about that upcoming. Dr. Butt will be here. It's really important. And again, if there's light chain, this is one of the things I'm interested to see what our speaker says. The big conundrum I have is light chain. We get the bone marrow, and they will do congo red, and they'll do in situ hybridization. But my concern is that that's not the affected organ. And my hematologist will fight. I just took the guidelines to the hematology, saying, you guys, you push back at me, saying, I think we need a cardiac biopsy. And we really do. And again, we send everything to Mayo for mass spec. It's formal and fixed. It's super easy. So you can take formal and fixed tissue. I don't even trust my local lab for congo red. Now, if it's positive, fine. Because I've had a couple where I go, like, I'm sorry. And I send it to the armed forces. Because we usually want to see that before we do paid Mayo Clinic, the money for the mass spec. But there really is important role. And that's why we have a dedicated talk to that. And the more important thing is also the false negatives as Nishan talked about. And I will say, as we're working on this project with Dr. Dev, where we're going back and we're doing automated screening using Davey score, I've come across patients that all these grade ones that we never pursued, I have a lot of patients that had a level one PYP or even zero that I still have a very high concern. Conversely, I had one of my patients that unfortunately went to heart surgery. They didn't do the biopsy. And we think his PYP was because he had a heart attack. So one of the false positives is myocardial infarction. And I'm old enough to say I remember the days when we used PYP, when we were equivocal about a heart attack. And it's often positive that with two to three week period. And so I had to re-scan because the MRI and all that. And I'm still a little confused because he has some sort of neuropathic process, but his genotype was negative. But it's very important. The role of biopsy is very important. And I'm glad we're gonna have a session on that. And I would just like to add two pearls to that because Dr. Warner alluded this to her slide. So there is a role for a non-tissue diagnosis, but as you learn this morning, 20 to 25% of trans-thermetine patients will have an MGUS. So MGUS must go under the skin. So anytime your patient has an MGUS, you must go under the skin. And I'd encourage you to target the tissue that is most affected. Because a fat pad is a potential tool, non-invasive, but the yield for amyloidosis, 70%, TTR. Some reports anywhere from 30 to 50, but I would say 100% sensitive and specific if it's in the heart, you can go there. I have one question from Carl Finley here. Thanks. So thank you to the team for the talk. You mentioned sort of, and this may be an unfair question, but you mentioned sort of some of the treatment options that are on the horizon that are around depletion. I mean, obviously we have stabilizers. And just from a thought process and mechanistically, what are your thoughts on maybe foreseeing what that might look like in terms of heart restructure or whatever the case would be as a depleter therapeutic? So I think this is hopefully the role of the clinical trial. I'm excited to see what these actually mean and whether or not we'll see some reverse remodeling. And I think Dr. Shaw actually alluded even to the world of stabilizer therapy. What we're seeing thanks to the work of Dr. Fontana out of the UK and others, we are actually seeing changes on these imaging tools in terms of the extracellular volume and things like that. So in the depleter trial, I'm curious, if these amyloid fibrils are really gonna melt away, what kind of cardiac reverse remodeling will that look like and what will that mean from a clinical, impactful standpoint? Because that's one thing to have remodeling, but if it's not changing quality of life, life longevity for the patient, I don't know. So I wish I had the answers, but I'm hoping the trials that are in the pipeline and are evolving in phase two and soon to be phase three will give us more answers. But they will be looking at those parameters. I think there's a lot of exciting things with one thing that I usually, I do follow besides my NTPRO BNP proponents, I follow prealbumin. And it's important that you know the effect of the treatment on the prealbumin, which is your stabilized TTR. I've had some patients start very low when I've identified with prealbumin levels as low as 12, but typically should be above 25. So if you're using a stabilizer, your prealbumin TTR should go up. When you're silencing it goes down. That's why if I have somebody in a clinical trial, I keep myself blinded. But what I think is fascinating is we're looking at gene editing is that we now have many years of experience with gene silencers in terms of safety, which was the biggest issue is vitamin A. And just with daily supplement, we haven't seen vitamin A deficiency. And again, as we pointed out that's about, you can silence about 90% of circulating TTR, but there's still separate TTR in the cerebral spinal fluid and in the corovary plexus that are not affected. And it's only the liver production. So we have good safety in gene silencing that we haven't seen vitamin A deficiency or other factors with those interventions. Just real quickly to go back to a point that Alberto made about myocardial infarction. I wanted to add one other thing that it's also true for acute myocarditis as well. So there's something about the sort of, post injury milieu that allows the tracers to sort of accumulate within the myocardium. So it's not just myocardial infarction, but also myocarditis. So there's important reasons for you to wait to do the imaging. And so I just wanted to add that piece. I will say that there are, as Julie mentioned, besides Mariana's data, there is some data from some of the other trials, some of the other silencer trials that suggest that there is at least some potential for reversal or at least stabilization of kind of at least measures by echo or other things. So imaging will help us understand whether or not we're at least stabilizing patients in addition to the important parts about saving their lives, obviously, and then giving them improved quality of life. So imaging, I think, is gonna have a much more important role as we get more and more therapies into the pipeline. This has been a wonderful discussion. I was just gonna mention one other thing about something known as seeding. We learned from liver transplant that we saw that people were seeding even after we gave them a new liver and that these therapies seem to prevent that seeding of normal TTR in these settings. So that's been an important thing that these interventions do allow breakdown of amyloid fibrils. Yeah, wonderful session brought to light so many of things that we know we know and what we know we don't know, right? The mechanism of how the neurotracers uptake becomes positive in TTR amyloidosis and the different conditions that can mimic this and hence clinical suspicion, high clinical suspicion should always be first step. Thank you. Thank you.