Good afternoon or good evening everyone and welcome to this webinar from the American Society of Nuclear Cardiology about interpreting and reporting F-18 PET and PI. So we're going to be focusing in the coming 90 minutes or so on floperidaz cases. Today I will be co-chairing this program. I am Maaz Al-Mallah from Houston Methodist and with Dr. Penita Shirintewati from Mayo Clinic and we have an outstanding panelist group that will comment on the cases that we will be discussing today. Dr. Tim Bateman from Mid-America Heart Institute in Kansas City. Dr. James Case from Cardiovascular Imaging Technologies also in Kansas City. Dr. Rob DeKamp from University of Ottawa Heart Institute. Dr. Marcella DeCarli from Brigham and Women's Hospital and Dr. Prem Soman from University of Pittsburgh School of Medicine. And today the goal is primarily to discuss the acquisition protocols, interpretation and reporting of F-18 cardiac PET perfusion tracers. We would like to discuss with you the uptake patterns that we see, incidental findings, normal variants for these F-18 tracers and how do they differ from existing cardiac PET tracers that we are currently using in the cardiac PET domain. We're going to talk about a systematic approach to review these images and finally look at how these cases and how these PET-MPI cases will help you either help serve your patients and provide you with the clinical information that you need to convey to the referring physicians. These are the disclosures of the faculty that you will have also available on the website. Through housekeeping requests, please respond to the poll questions that will be coming later on and then close the poll. There will be about six questions. You may need to scroll down a little bit to answer all of them. Please assist us by entering your full name as you registered on your Zoom display. So we would like to see first name and last name so we know the attendee. Be sure to mute your personal phone and mute your computer audio and so there is no disturbance in the background. You can send us questions and we want this to be very interactive please. So send us questions by using the Zoom chat button. So at the bottom of your screen or in the top of your screen you should have a Zoom chat button. Please click on it, enter your questions and we'll be happy to the panelists will see your questions and we can either answer them one by one or we will answer them verbally so everybody can see them. At the end of the conclusion of this program you will receive a link that you can use to claim your CME. The link will open at the conclusion of this program and will be emailed to you at the end of this program. I want to thank all ASNIC staff and I want to thank everybody who helped make this a reality and I want to also thank Dr. Philip Mora who is going to be our social media ambassador for this program. We'll be tweeting on Twitter and other social media venues and this program is was made possible by an educational grant from GE Healthcare and we thank them for their support. Again I want to thank all ASNIC staff, ASNIC leadership for making this a reality and help us in putting these cases together. At this time I'm gonna stop sharing and I will ask Dr. Benethia to start a quick presentation about the program, about how to acquire and basic findings from the F18 MPI findings and then we'll go ahead and start reviewing cases. Benethia. Great, everyone can hear me okay? Yes, we can hear you very well. Great, thank you so much Moaz and hello everyone. It's a pleasure to welcome you to tonight's webinar and a warm welcome back to those who also joined us for our January session and as Moaz mentioned I'm Benethia Charentaitoui from Mayo Clinic in Rochester, Minnesota and I also have the honor of serving as the current ASNIC president. It's truly a pleasure to co-host this session and be a part of what's a transformative moment in our field. So as Dr. Almala mentioned, after more than 20 years without a new FDA approved perfusion tracer we now have F18 floperidaz. So it's an exciting development with the potential to broaden access to cardiac PET and enhanced diagnostic capabilities. So this really marks a notable evolution in nuclear cardiology and I'm really proud that ASNIC is helping lead the effort to bring this innovation into clinical practice. So as Dr. Almala mentioned, tonight's session will focus on image interpretation and this is an essential step now that the tracer is available and again this is just the beginning because ASNIC will continue to provide practical tools, educational programs and clinical guidance to support successful implementation of the tracer across diverse practice settings. So we have a stellar panel of experts with us this evening and I'm confident their insights will be both practical and really impactful. And so before we dive into the images, I'd like to take just about eight minutes to provide you with an overview of the unique properties of F18 floperidaz and the protocols associated with its use. And this is the structure of F18 floperidaz. It's derived from the pesticide paraben. It works by binding to mitochondrial complex 1 in the heart. Now floperidaz has several favorable characteristics. First, it has very high first pass extraction fraction over 90% and this has various benefits including the ability to identify milder perfusion defects and greater accuracy in reflecting the true extent of defects as compared to technician labeled tracers. And so F18 floperidaz also has a linear relationship between tracer uptake and myocardial blood flow with a strong correlation with radioactive microspheres in determining absolute quantification of regional myocardial blood flow over a wide range of flows. There's very little roll-off phenomenon at high flows as shown here and this promotes not only accurate flow quantification but also less underestimation of ischemia. Floperidaz also has the shortest positron range among the commonly used PET perfusion tracers at 0.1 millimeter in tissue and a shorter positron range is better for both image quality and flow quantification. It also has the longest physical half-life at 110 minutes among the commonly used PET perfusion tracers. So all of these favorable characteristics of floperidaz, the high extraction fraction, linearity with flow, short positron range, and long physical half-life all contribute to several advantages and this is particularly true for superior image quality. So you have higher count statistics, high spatial and contrast resolution, greater defect resolution as compared to SPECT, and we'll go over some of these defects and reversibility are more readily identified and so there's greater interpretive certainty. And in terms of diagnostic accuracy in the Aurora trial, the phase 3 part 2 study that led to FDA approval of floperidaz for overall detection of epicardial CAD that's defined by 50% stenosis, sensitivity and specificity of floperidaz PET were significantly higher than the pre-specified threshold. Sensitivity was also higher for floperidaz PET than SPECT and this is in all comers in women and in those with BMI greater than 30. At the same time, specificity was non-inferior between floperidaz PET and SPECT MPI. Then operationally, the longer physical half-life of floperidaz of 110 minutes has the advantage of facilitating availability of the tracer for unit dose distribution from regional radio pharmacies so that practices don't need higher cardiac PET volumes to be economically viable. They also don't need an on-site cyclotron since the tracer can be shipped from outside facilities. There's also the advantage that floperidaz can be combined with exercise treadmill stress because of the longer physical half-life but with exercise we will lose flow. We also need to acknowledge some of the current opportunities or challenges with floperidaz because it's a new tracer. Clinical experience is still relatively limited but this is rapidly changing with at least 30 sites expected to come on board soon. There are new imaging patterns we'll need to become familiar with and we will go over these. I've listed them but we will go over these throughout this session. We also need to be cautious about over-calling subtle defects given the changes in image appearance and that milder defects may appear. On the more practical side, floperidaz is associated with a somewhat higher radiation dose compared to other PET perfusion tracers, perhaps higher per patient cost and the availability initially may be a little bit limited. And then currently the protocols are less efficient but there are efforts underway to streamline acquisition and improve efficiency so stay tuned for that. So speaking of protocols, here is the pharmacologic one-day rest stress floperidaz PET-CT protocol that was used in the phase 3 part 2 or Aurora trial. And so this is what's in the package insert and following the CT scout and transmission acquisitions, 2.5 to 3 millicuries of floperidaz is injected and a single ECG-gated 15-minute dynamic LISMOD acquisition can be performed. And then after the resting acquisition is completed, we can get ready for the stress but we need to wait at least 30 minutes between the rest and stress tracer injections for pharmacologic stress, 30 minutes. Once the appropriate time has passed, we can then give the vasodilator stress and then 6 to 6.5 millicuries of floperidaz and then another 15-minute ECG-gated dynamic LISMOD acquisition is performed. So the total time is about one hour but we need to wait that 30 minutes. Again, there are efforts to shorten and make the protocol more efficient. A couple of additional key points, the total activity should not exceed 14 millicuries for an individual subject and floperidaz and adenosine should be given through separate lines or separate ports of the same IV line, the rest I've already mentioned. The one-day exercise for pyridaz protocol takes slightly longer because with exercise, the rest and stress tracer injections need to be at least 60 minutes apart. And then the image acquisition will also, for stress, it will need to start 15 to 25 minutes after stress injection. So we have to time this. And again, we cannot currently measure myocardial blood flow with exercise treadmill PET. But several groups are working on testing more efficient protocols and also maybe trying to estimate flow without the initial bolus injection. Also remember that during exercise, the patient should continue to exercise for an additional one to two minutes after the floperidaz injection as much as possible. So when Dr. Almala will start to show us normal F18 floperidaz images, you will see the following. First, the LV myocardium will be better defined than what we're used to seeing with spectrum PI and with rubidium. Images may look a little bit more like N13 ammonia images if you use N13 ammonia. The myocardium will appear thinner and the LV cavity will appear larger. Second, the count distribution will be more homogeneous. But there could be some subtle defects that we need to be careful not to overhaul. Capillary muscles are often visible. We see them more with rest than stress. And then anatomical apical thinning is present in most cases. Dr. Almala will show you examples. This is very important. Subdiaphragmatic activity may be present but usually does not interfere with interpretation. RV uptake is often present in normal floperidaz images. And then there's usually clear segmental brightening and excursion on normal gated floperidaz images. For abnormal floperidaz images, defects are more evident and reversibility more readily identified with higher interpretive certainty. And with pharmacologic stress, the EF and wall motion may decrease with stress in abnormal studies. TID may be more evident with floperidaz, but currently we do not know the TID ratio threshold to use. This is also being worked on. And then the effects of misregistration or motion may be more pronounced. So this is my last slide now. And we're going to go to the poll before Dr. Almala starts to show the F18 floperidaz images. So if you could answer these questions, we would really appreciate it. And then once we'll give it a moment here. And then just a reminder, please put the questions in the Q&A, not the chat. The chat will be disabled for everyone. And we will try to answer the questions as much as possible. And we'll have a discussion if something is not clear or needs more emphasis. So thank you very much. And when we're ready, I will stop sharing and we can go on to the cases. All right. Thank you, Panethia. And we'll give the attendee a few seconds to answer these questions. Hopefully, it will give us an idea about our audience tonight. So again, we're asking what best describes you and whether you are doing cardiac path. How long have you been doing it? What's the volume of your studies in a month? And what type of machine do you use? And how old is your machine? And finally, if you are using Flipgrid or you are thinking about it. All right. We'll give it 10 more seconds. And then when you're done with the poll, if I could have just any one of you just send a test. Oh, there we go. I wasn't sure it was working. Thank you for sending, Dr. Kaldon. I only saw the first question. You had to scroll. Scroll down and then it will take you through the questions. There are six questions. All right. Okay. So if I may ask my panelists to please turn on your cameras and we're going to start showing cases. Again, I would like to welcome all of them as I introduced them earlier. And Dr. Case, Dr. Soman, Dr. Bateman, and Dr. DeCarli. So let me share my screen. This is the first case. As always, the first case is going to be a normal case for many of you, but we're going to go through many nuances that Dr. Panethia mentioned earlier. And we're going to look at some of the nuances. And it's very important. I know many of you have been doing PET. Some of you may not be doing PET. So we're going to spend a few minutes on systematic approach to interpreting cardiac PET, and this is a PET CT. So I'm going to start with Dr. Bateman. If you can just walk us on, like, what do we look at in the very first assessment of our cardiac PET? Yeah. So similar to SPECT imaging, you know, step number one is always to be comfortable with the quality of the study is worthy of interpretation. So with SPECT imaging, you know what those parameters are. We look at the rotating projection images and we look for evidence of attenuation artifacts and so forth. With PET, there is so much attenuation from the body with PET tracers that we need to do in everybody attenuation correction. And most commonly, we're using CT to generate the attenuation map. And then we have to be sure that that map is registered properly to the emission data. The task is actually made a little bit simpler with FLIR-PIRIDAS, because as you can see, the emission image is spectacular. You know, the counts are very rich as seen in the yellow or orange there. And in this normal case, they're very uniform as well. And we want to make sure that they fit nicely within the CT image of the myocardium and are not moving outside of that into either lung field or further into the mediastinum. So we always look at these images and not sure what else to say, but it's important that these be registered properly. If they're not registered properly, you know, additional work needs to be done to do that. That's something that your technologist needs to do. But you need to communicate with them if you have concerns that the myocardium is not well within the, that the emission data is not well within the myocardium. Yeah. And Dr. Case, in terms of misregistration, like how much, because with FLIR-PIRIDAS, I mean, what Dr. Bateman just mentioned is something that we do with every PET scan. Would it be more important for us to be very careful with FLIR-PIRIDAS or is it more forgiving if there is minimal misregistration? Yeah, the high resolution of the FLIR-PIRIDAS, it's a bit of a double-edged sword in that on the one hand, when the quality stuff works out, the images can be as we have in this case, just spectacular, but it's going to be much more sensitive to issues of patient motion. And I know we have a pretty diverse group here. This getting the heart registered within the CT map is important to do prior to reconstruction. If you're coming from more of a general nuclear medicine background, you might be used to doing fusion where we're just scooting the emission and transmission data relative to one another. These re-registrations have to be done prior to reconstruction. And then the shifted data has to be put back through the reconstruction algorithm to take out those artifacts. And so it's very important it's done on the camera with the technologists before it gets to you. And if you see a problem, it has to go back to the camera to get it fixed. Okay, thank you, James. And yeah, so what we've mentioned so far is that this is an important step for every PET tracer, but it is especially important for flipididase given the high-resolution and positron range. So we're gonna move on to the static images, and I'm gonna ask Marcelo to walk us through this. What would you do if you like this color, or I can give you another color scheme? Thanks, Moaz. And okay, so here we have the typical display of our three axes of the heart. And one thing that will be immediately clear is what Benicia was mentioning during her presentation that you could immediately see that the counts in the apex are lower than in the rest of the heart. And this is related to partial volume effects in the apex, which will be a lot more noticeable with this tracer compared to rubidium if you're doing rubidium. So you just have to be aware that this is sort of something that we'll see commonly. Now, not every apical defect will be partial volume, right? There could be defects that are real, one clue is to see if what you see is reversible or not. In this case, the defect seems to be pretty fixed. One trick that we sometimes use is we go to the gated images and we look at the ancestral frames and see if we can achieve resolution of the defect as the myocardium gets thicker, the partial volume effect will become less impactful on what you see on the recovery of the counts. And you can see that in encystole, there is filling of that apical defect. And so that's one trick that you can use, but I think in general, the principle is that apical thinning and partial volume in the apex is a fixed defect, it's not something that is reversible. If it is reversible, you have to begin to think that maybe there is something real there. If you can go back once to the general images and then the way we systematically approach the reading is I usually like to start at the apex and we just spoke about that. And then you go the same way you do it on your SPECT images. You will go to your short axis images and you go through the left ventricle and try to use the other axis as confirmation. And in this particular case, we see that the images are pretty homogeneous. You see amazing resolution with the papillary muscles clearly visible there, but there's no evidence of perfusion defects. So this looks like a pretty normal looking myocardial perfusion scan. Excellent, okay. And the papillary muscle that Dr. Panethia mentioned, it is more prominent for reasons still unclear to me. It's more prominent on the rest images. We see it sometimes on the stress images, but I don't know what is the value. I mean, if it means anything that you don't see it there. And yeah, let's move on to look at the gated images. So I'm just gonna load the gated and maybe I'll give it to Dr. Soman to walk us through gated images. If you want this view or I can provide you another view. No, this is good. Thanks, Moaz. And again, as you do for other tracers and as you do for SPECT, you're looking for brightening of the myocardium, which means thickening. And that is an indisputable sign that that area is functioning and is alive and well. And here you see that all the areas, all the segments of the myocardium are thickening. And you see that the EF at rest was 61%, and there's a robust increase in the EF on the stress study to 72%. Now, for those of you who've been using rubidium, we have more definitive criteria for what is considered an adequate EF response. Dr. Ducali's group and others have shown us that if the EF response is 5%, that is a good prognostic indicator and sort of excludes extensive coronary disease. Now, with ammonia, and I think with flupiridaz also, we don't have definitive quantitative cutoffs as to what is an adequate response. I do ammonia, and certainly we want to see some sort of response and definitely not a decrease in the EF. And so here, of course, there's no ambiguity here. It's a very robust EF, and that's very reassuring. So you see that increase in EF, even though this is a vasodilator study. Thanks, Prem. Maybe I'll ask the faculty who ever wants to answer this. We see the RV here. I know Panethia mentioned that in the beginning. Is this normal, abnormal? Maybe Marcelo or Tim? But it looks pretty normal. What you see thickening there in the middle of the RV-free wall is the moderator band. It's a thicker structure that, you know, you could see it more prominently in systole, but it looks like the RV-free wall moves normally. And, you know, the quality here, you know, we know, you know, I think this will be an interesting area for this tracer that, you know, perhaps we could use the first pass of the tracer through the heart to actually get an RV ejection fraction, which I think will be quite valuable from a tracer like this. So for many of our attendee, if like, you'll often see the RV, and that's what Dr. Panethia also mentioned in her slide deck. So that's within the normal. And if I zoom out, even on the static images, you see it, and this is a moderator band that Marcelo was talking about. And this is the subdiphragmatic activity that you also see there. So you see some uptake and deliver and other, which is less pronounced on the stress images, as you see here. Okay, and finally, since this is a SPECT CT, one of my favorite areas is don't forget to look at the CT. So that will provide you with some information about atherosclerosis. So we can look at coronaries, and this patient's clearly no calcification in the LAD area, none in the CERG, and none in the RCA. So another healthy looking CT, no abundance of subcutaneous fat and otherwise. So this is all reassuring. All right, we're gonna move on to the flow part of this study. So I'm just gonna load it up, and maybe I'll ask- Can hear you. Can you hear me? Yes. Okay. Yes, no problem. All right, so we're gonna go, I see Rob here. So maybe I'll start with the quality assurance for the flow. I don't know, Rob, if you're ready to start looking at what are the quality assurance things that we need to do in general for PET, but also what are the specific things that we need to do for flow for fluperidaz quality assurance before we go to the numbers? Okay, very good. Thank you, Mamas. So with any flow assessment, you wanna make sure that you review the motion. So thank you, you have played the Cine button so you can scroll through the individual frames. You wanna see that the LV contours are tracking the ventricle well through all of the frames, and that there will be a secondary region placed in the blood pool, which you can see with this program is right at the valve plane. You wanna make sure that that blood region of interest is well-centered on the early peak activity. So maybe if you could possibly stop and scroll to one of the early frames where we can see just the peak blood activity, right? So at rest, you can see that peak activity comes around frame four. At stress above, the peak looks like a little bit earlier as the transit will be a little bit faster. You can probably go back maybe one or two frames still to get the peak brightness in the cavity. Okay, I guess that's about it. There must be a bright spot somewhere else below the images that's affecting the scale. So you wanna check that that's well-centered over the peak early blood activity, and also that it's not substantially overlapping with any of the adjacent ventricular activity, either in the anterior-posterior or on the HLAs, not overlapping with the septum or the lateral wall. So that's the region placement. And then looking at the time activity curves below, you want to make sure that you have at the start of the time activity curve, so you'll see two curves, the green curve, which starts at zero and rises and then falls back down. That is the activity in the arterial blood. And you need to ensure that the full rise, starting from zero activity is captured to the peak and then following the clearance curve. So it's very important to have at least, at rest, at least one or two points with zero activity, and then similar at stress. Now, for fluid periodontitis in particular, for a same-day protocol, there will still be some residual activity left over from the rest scan at the start of the stress scan. And you'll see on the top of the panel in this particular program was a function to subtract the rest residual. And you can see that that had been applied. Now, Moaz has turned it off. And you can see again that at the starting frame, there is still, you know, the activity is not starting at zero. And without doing that, the stress flows would have been incorrect, kind of inaccurate. I don't know, Moaz, if you can see what the flow value was before correction, 3.7, 3.7 globally. Oh, for stress flow, right? And then after correction. It's gonna come down to about 3.5, sorry, to 2.7. And almost for the flow. Can you re-enable? Yeah, it's coming. 2.7, so quite a drastic reduction. And so it's very important to make sure that whichever program you're using has an ability to do that accurate background subtraction. Okay, so yeah, to sum it up. So if we're gonna go back, we're gonna first wanna make sure that it's a good injection. We captured the entire input function. We wanna make sure that our contours cover the myocardium. The ROI should be where it should be for that program. This is for any kind of PET activity, and there is less like motion. If there is motion, that's corrected. But in flaperidase specifically, I think we need to go ahead and do the residual subtraction because not all the rest of those have decayed. So with that, we get now the accurate blood flow, and this is what you see here. And maybe Marcelo, I'm gonna ask you to like help us interpret these. Okay, yeah, so I think Rob did a great job already in illustrating all the quality points that you need to go through to make sure that you can trust the numbers that you're getting. But one thing with flaperidase is we really don't know what the normal value is. We don't know what the normal values will be, but generally speaking, I think the values that you see in all coronary territories and globally on the stress flow are pretty normal for someone who is, I don't know how old, but presumably a middle-aged person there. The values on the stress flows are gonna be very low, very normal. And then the flow reserve is certainly within a completely normal range. So with this information now, we have normal perfusion images, no evidence of regional perfusion abnormalities. There was no calcium moass. No calcium. There was no calcium, and now we have a completely normal response of the microvasculature. And so in the report, we would conclude that this patient does not have evidence of epicardial flow-limiting coronary disease or microvascular disease. So I think this would make it all consistent data and very reassuring for the referring provider and of course for the patient. I think it's very important that when you report this out, you actually not just talk about flow-limiting coronary disease, but also the microvasculature. I think this is a common question that physicians will have. The guidelines themselves at ACC and AHA suggest that if you're using PET, that you need to do quantitative flow to provide that comprehensive physiologic data that we can assess with PET. Okay. So this is good, and this concludes the first case. Let's move on to the second case now, and let me show this. So we're gonna now look at case 5070, which is on your sheet, and this is an exercise study. So this kind of highlight of some of the things that we were not able to do with rubidium. So this is on the second page from our list, and you can see here it was a SPECT-CT, so we're gonna start systematically as we did before. I'm gonna ask Tim to also walk us through the quality, but also later on go through the interpretation. Yeah, sure. Well, so first of all, you can actually see on the perfusion pattern here that things aren't quite the same as they were in the prior one that had uniform counts throughout the myocardium, but there's some marked reduction in counts in the anterior wall and the portions of the apex. But in terms of the quality control, again, it looks very excellent. It looks like it's registered exactly the way that we want it to be registered. It's a little bit more challenging sometimes when you've got reduced counts, like you can look at the coronal view on the right side panel there. Mouaz, if you wanna take, yeah, take your pointer over there. You can see that it can be a little bit challenging sometimes to know whether the myocardium, whether the emission counts are outside of where we want them to be. That looks better. I think I would accept that as being satisfactory. So from the quality control standpoint, I think we're okay on this study. All right, so this is an exercise study done via the protocol that Dr. Panethia mentioned. And how would you look at this? Yeah, so the good news for this person is that the resting images look pretty good. We're gonna be looking again at the apex very carefully because it is de-emphasized substantially. So we're gonna wanna look at the motion and so forth to be sure, but we're not seeing any signs of significant myocardial infarction in the rest images. In the stress images, we have a very large perfusion abnormality that extends from the apex all the way up to the base of the heart. And it's affecting the anterior wall and the septum throughout a little bit of high lateral wall as well towards the base of the heart. So one would assume that what we're looking at here is a very large LED territory ischemic defect Okay, you can see there's transient ischemic dilation that's quite substantial. And there may be some motion in this study. You can see the shape of the ventricle is quite different. It's kind of oblong at stress, it's appropriately rounded at rest. That may be secondary to ischemia or it may be reflective of some motion early post-exercise. We're supposed to wait about 15 minutes post-exercise before we start to take these pictures because the person is often hyperventilating post-exercise, the diaphragm is moving up and down and there can be some motion contamination of the images. Yeah, this is still a high quality study and there clearly is some TID here. Yeah, although the TID cutoff is coming to be 1.05, but probably as I totally agree, there is visual TID that you see there. Right, yeah. And so just a clarification for the protocol, it looks like as Benetia mentioned, the time between the two injections has to be a minimum of 60 minutes between stress and rest. So now looking at ejection fraction. So just related to that, Mouaz, so I guess in terms of the perfusion, do you think waiting 60 minutes would affect, it certainly will affect function, but will it affect TID ratio? That's interesting to know. I don't, I mean, it will be interesting. I mean, with this degree of ischemia, there is visual TID. To me, this is a high risk scan and this is large amount of myocardium that's jeopardized. What do you think, Prem? You're muted, Prem. Certainly, yes, you know, I think the question is, will the ischemia resolve and function improve if you wait long enough after the stressor to image? And we know that, you know, the degree of post-ischemic stunning is a function of the degree of coronary stenosis, and to some extent, the extent of ischemia. So I don't think that in somebody with such extensive ischemia, that will be a problem. But it's a valid question. I think the longer we wait, the more likely that function is likely to recover, exemplified by SPECT imaging, you know, where you may not see a wall motion abnormality by the time you acquire the image. And here, again, I think the LAD defect goes all the way up to the base of the septum. And as Tim mentioned, it probably is a proximal LAD type of lesion. Yeah, now, another important issue here, I think, is that we are a little bit hampered here, just as we would be with a SPECT study, that we don't have flows. So we can diagnose that there is a large area of ischemia in the LAD territory, but it's much more difficult to know what's going on in the lateral wall and the inferior wall because we don't have flows. So if, for example, we knew that this patient had an occlusion of the LAD, but it was surviving, the muscle was surviving because of rich collaterals from another vessel, it would be very difficult with exercise PET, just as it is with exercise SPECT, to know whether the subtending vessels were developing significant disease. So that was one of the questions from the attendee, actually. Is there anything that may be worth just spending a minute or so talking about? Do we prefer pharmacologic stress or exercise when we have the ability to exercise? I think the value proposition of PET MPI is MBF, myocardial blood flow. So in my mind, I think pharmacologic stress is preferred. But there may be instances where we will want to exercise. So maybe, I don't know if someone wants to take this question. Yeah, I think that if it's a fairly straightforward scenario, I think exercise would be fine. But if we knew that a patient has, if we already knew that a patient had single vessel disease and we were asking about the other territories, I think that I would much prefer pharmacologic stress with flow to exercise. You know, Tim, I agree. And I think as a specialty, we have always proposed that for people who can exercise, you should put them on the treadmill because exercise, the exercise capacity is such a powerful prognostic indicator. MUAS actually has shown that unless somebody has a very good exercise capacity, which is a very powerful prognostic indicator, but anything less than very good, then the flow data actually is better for prognostication than the exercise time. So, you know, we may, now that we have such powerful tools like flow that is becoming more and more available, I guess we have to rethink. The other thing, of course, is it's easy to put somebody on a treadmill to get the exercise capacity, even if you have to put them on the treadmill and then do a vasodilator study. That's easy to do. Okay, so to summarize this case, we also saw a 2% drop, but the degree of ischemia is large. So as Tim mentioned, there is no doubt that this is a large, at least single vessel disease, but short of having flow, we may not be able to assess non-obstructive or obstructive disease, but less severe in the other territories. And I think, in my opinion, exercise would be very helpful, for example, for patients with anomalies, with bridges, or if you don't, or like if you really want to do the test and the patient has contraindication to vasodilator stress, but I agree with all the comments that have been made that the value proposition of cardiac path is flow, and it's going to be very helpful to get that. Anyone else want to add anything while I'm switching to another case? Well, you could show the gated, the apex and the rest images again, just for, because the apex is challenging in any of the high resolution studies that we're doing today, whether it's with CZT or with ammonia, and now with Pyridaz, with digital PET, with rubidium, it can be challenging too. But you can see the apex at rest is brightening and thickening very, very nicely, and it makes it easy to know that there's no infarction at the apex. Exactly. We don't have the comparison here to specced, but I would just make the point that defects tend to be very easy to identify, generally more evident, and in the trial, we saw greater defect resolution with abnormal fluid Pyridaz as compared to abnormal specced, and so there's higher interpretive certainty. I just wanted to make that point. And yeah. Yeah, I would agree. The interpretation of the study is not particularly challenging, is it? No. It's nice. It's nice. And now that you guys asked about the spec, this is the spec of this case. Oh, yes. Okay, great. So let me just double check. Yeah, this is the case. So this is a PET, and this is a spec of this case, which, like how many think this is abnormal versus normal? I mean, it's abnormal, but not as impressive as what you see. Come on. That is, you know, that is a defect you can see from the back of the room, so. Okay. But there was more reversibility, I think, with the PET. And this patient had the CTO of the LAD. All right. I'm going to stop from one computer. We're going to switch into another software package. When you're doing that, could I get the panel to comment on, especially James, on the start of the scan time, especially for stress? I think a couple of attendees asked and made comments. There are really two points, and Rob's put them in the chat and had a pretty good explanation there. The first thing we want to do is we want to make sure we're measuring blood flow. We capture the entire input bolus. We use that input bolus and the counts that's in the blood to effectively normalize the uptake that we see in the myocardium. So if we miss some of it, it can cause the blood flow calculations to be artifactually high, potentially masking any kinds of defects. So that's the first thing that we want to do is we want to make sure we start the acquisition time before that bolus comes in. Now, Rob pointed out another interesting fact about imaging with Flerpyridaz, in particular same-day Flerpyridaz, is that we also need to subtract the residual resting data that may still be there, because remember, we don't have a 76-second half-life with this agent. We have a little short of two hours with this agent, and we're not going to be waiting two hours between the two studies, or even more, to let that rest decay. So we're going to have some of that contamination from the rest coming into the stress data. So we need to subtract its contribution before we do the blood flow calculation. So we need to have counts in that early frame to capture, to make an effective measurement of that residual rest so we can remove it from our calculation. All right. Thank you. Thank you. Now, just I know different people use different software, so we're just going to show you the same thing on different software packages. So this is the CDER software, and again, this is a case, the label of, yeah. So this is a case that's labeled BMS005, and so you have it on your list, and okay. So looking at the quality, looks well-registered and appears to be okay, we check it. So from now on, we're going to move, like, the quality has been checked unless there is a specific quality point that we want to make. So maybe I'll ask Marcelo, or if you want to walk us through here what you see. Yeah. So okay, so there are a few findings here. Number one is the LV cavity dilates, you know, with stress. You can see TID ratio there on the right calculated at 1.44, but regardless of the number, you can visually see it very clearly there. And then the images show, like in the last case, a very, very large and severe perfusion defect involving, you know, the LV apex, the anterior and the anteroceptal wall from base to apex, and there is complete reversibility, you know, again, consistent with severe ischemia throughout the proximal LAD territory. One additional finding that one can make here is that, at least to my eye, there's a little bit of increased right ventricular tracer uptake, you know, on the images, on the stress images compared to the rest, and that would be another sort of high-risk sign, right? We have a TID. We have a large perfusion defect. We have transient increase in RV tracer uptake. All of those are high-risk signs, you know, that add to it. So I think it's a pretty straightforward interpretation in this one. Okay. Now, what about ejection fraction? Oh, okay. So you're going to ask somewhere else. Yeah, go ahead. Like, go ahead, Marcelo, and then we'll ask Prem about the flow. Okay. So, you know, on the gated study, one can see that there is obviously less thickening in the ischemic area. You know, it's always hard to judge when you don't have many counts, but I would, you know, I don't know that there's a wall motion abnormality. It's just hard to see because there's no counts. And then the ejection fraction, so where's the number? So I see a number, 68%, but this is for what study? So the rest was 76%. 76%, going down to 68%, which again, not very surprising based on the findings that we had when we looked at the perfusion images. So now we have a full house of high-risk findings. We have a very large perfusion defect. We have transient dilation of the left ventricle. We have transient uptake in the RV, and now we have a drop in ejection fraction. So, you know, clearly all consistent with severe and extensive ischemia. Okay. And now we're going to ask Dr. Soman, can you tell us about the flow? And we did apply the correction. So we did correct for residual, we correct for motion. So yeah, the motion correction, sorry. So all the QA metrics have been checked. And so you have the flow here. And if you look at the polar maps, you have the territorial flow. And I'm looking for the global flow. Where is that? Okay, that's great. That's great. So I usually look at the resting flows to make sure that they are within the normal limits of whatever is considered normal for that program and in your lab. For us, it's somewhere between 0.6 to about 1.2. And you see here that the flow is normal, the global flow is normal, and the territorial flows are normal and sort of homogeneous across the different territories. If you see one area of the resting flow is much higher than everywhere else, you have to try and figure out why that is. Usually it's spillover from some adjacent activity. Now, if you look at the peak stress flow, the global peak stress flow is very reduced. So we use a cutoff of about 1.8. And again, it's important not to use absolute binary cutoffs. It's about 1.8. This is well within the abnormal range. And the flow reserve, which we use about 2.0 as the normal. So you have normal resting flows, very abnormal stress flows, and an abnormal flow reserve, which is consistent with obstructive disease in the LAD territory. Now, the advantage of flow, of course, is you can look at the other territories and see what's happening there. And here you see that the—look at the territories, myocardial flow reserve, both in the circumflex territory and the right coronary artery distribution. The flow reserves are normal, which means that, you know, there's—it's very unlikely that there is obstructive disease there. Now, if you look at the peak stress flow, they're slightly abnormal. Now, sometimes, if you have a large LAD territory, sometimes a bit of the lateral wall and a bit of the inferior wall can be included in that LAD territory. And the computer will erroneously attribute that to the circumflex and RCA territories. So you have to be careful when you interpret it based on the computer's allocation of territory. So here, I would just say that, yeah, I think the flow is relatively normal in the circumflex and RCA territories. So this mostly looks like single-vessel LAD disease. Rob Dickamp, Dr. Dickamp, anything you want to add here? Is he muted? Yeah, just unmute. I don't have anything. Okay, sorry. Do you have anything to add on this case? I have something to add, actually. I think that we are learning a lot about flow with each case that I see, especially abnormals. I am learning a lot about flow. And I think there may be some nuances. Prem, you kind of use, I think, what we have used for N13 ammonia rubidium for absolute flow and flow reserve as sort of our threshold. But I wonder, as you show more cases, I think we may have to, it may not be the same. And we've seen with other, for example, O15 water as well, that we may have different thresholds, different cutoffs kind of for normals versus abnormals for O15 water and also for stress flow. And so I think this is something that we're learning with each case and maybe just have to kind of temper a little bit with what we're doing. I don't know if others want to comment on that. Yeah, I think, I mean, none of the tracers are actually changing the underlying flow. It's the models for those tracers that may or may not be that great when we're talking about this big a range that we're trying to cover blood flow from. So my guess is there's a lot of work to be done. We've never had a tracer quite like this that can go to have such a linear uptake across such a wide range of blood flows. And it does give us a tool for really understanding blood flow at a level that we hadn't been able to see before. So there's a lot we're going to learn in the coming years with this. But as to whether the tracers are different, they're not really changing the flow itself. That's the regadenosin or dipyridamol, whatever it is you're using in there. But the results we get out of the software will be different because the models are different. All right, Rob. Good night. Sorry, let me just give it back to Rob. I asked him before and... Go ahead, go ahead. Just going to add the comment. I think that I agree that the peak flow values for this tracer or the, what should I say, as James said, the measured or the reported peak stress values depending on extraction properties of the tracer and the model, you know, are not as well studied yet as the relative perfusion image interpretation that was used for approval of the, you know, for regulatory approval of the tracer. And certainly there will be more comparative studies being performed and coming out. For example, comparing Pleur-Pyridaz with O15 water, you know, as a gold standard. So we should follow this closely, I think, still in the emerging literature. Although I have to say that we've been using it and I think, let's put it this way, where it is low, it is low. And where you expect it to be high, it's expected that you find it high. It's just the cutoffs that are not very clear. So, and again, whenever you draw a cutoff, one point, if you draw a cutoff at 2, 1.9 is not very different from 2.1. So I think you have to look at it. But again, in this case, for example, we have a large perfusion defect and I see in the LED, my peak flow is 0.9, while in the CERC and RCA, my hypodermic flow is 1.6. So I'm very confident that the RCA and circumflex look pretty good compared to what we see in the LED here. And it's pretty reassuring. And even if you look at the flow reserve ratio. So I think overall, it's heading in the right direction, whether this, you would like it to be 1.7, 1.8. That's probably going to learn more with the day. But at least where it should be high, we're seeing it high. Where it should be low, we're seeing it low. Okay, I'm sorry. There was one, I think James or Prem wanted to say something. No, no. I was just going to make a quick comment that rubidium and ammonia are so very different in their extraction fraction and linearity, right? But we use the same flow cutoffs. Yeah. And maybe fluperidase and ammonia is the same difference as rubidium and ammonia. And so I think I agree with Muaz that the patterns are more different and the relative differences are perhaps more different. And using these absolute binary cutoffs is probably not a good thing anyways. All right. So I want to start doing now some more just focus discussion on certain areas. And let me just make sure I pulled up the right cases. All right. So what do you think quickly? Maybe I'll give this to James and then Rob if you want to comment further. So rest in the lower part, stress on the upper part. And we see this defect and if we were looking at it systematically this is your fusion data guessing it might be a physics question james yeah it's kind of sounding like it isn't enough yeah um well this is uh this is one where where we have a ct image which isn't which isn't that great um you can see the little little chips they're little chips along the medial spinal edge uh the heart seems to be laying out into the lung field um there are really three things that uh that make up what i would call a good transmission study for attenuation correction the first one is we have a well-defined boundary is we have a well-defined boundary between the heart and the lung the second one which really isn't that big of an issue with uh with pet ct unless you have metal artifacts is you have uh pretty much water attenuation coefficients in the medial spinal region and then finally finally the uh the heart is well placed inside of they're not overlapping into the lung we're not excessively uh uh moved uh towards the right side and over correcting so in looking at this image it kind of fails on two of the three tests we don't have a nice uh we have kind of this this little sawtooth effect and this can happen in studies where the uh where you have a low number of slices like a 16 slice machine in each one of the passes captures a small amount of volume and you end up with this sawtooth appearance along the medial spinal edge and the second thing you can see especially as you get more to the base on the lateral wall some of that uh some of that that heart activity is hanging on the lung we do attenuation correction the attenuation correction is there to try and recover counts that are lost to uh the soft tissue but in this case if we attenuation correct with the lung which is has about uh anywhere between a quarter and a third the density of soft tissue we don't get as many of those counts back and so we lose those counts and it gives the appearance of of a drop in activity so all those things work together if we want to go back over to the um to the slice images to what we see here we have have kind of a strange looking um uh you you a strange looking image or strange looking appearance to the anterior wall uh in the lateral wall and you you really have to well it really bothersome things about it these misregistration artifacts is they they can look like real disease like this sure yeah you could talk yourself into a diagonal um or or circumflex or even uh you know in some cases they look like left main uh type of thing so it's it's not the sort of defects you can sweep under the rug readily so so that's why we have to inspect it the other thing that we saw in this one is because for period as is a higher resolution agent this is this is a small amount of misregistration causing this defect not even the thickness of the heart is enough to to bring down those counts so that's that's um my sense of rob uh what do you think looking at this particular study yeah thank you um great um observations james um i would just also i guess point out um on the images themselves of course it's unusual to have a resting defect that improves at stress so you know that's one hint that would make you think about um an artifact um and yeah second the attenuation misalignment um of course most commonly observed in the anterolateral wall because if there is misalignment um it needs to be corrected on the scanner console this is something that your technologists will need to learn to do um and um you know there's a learning curve there for sure and so you know sometimes it could it can depend on the diligence of the technologist um and the last point you know relating to what you described on the characteristics of the ct itself um would say you know if you're doing a slow ct on a scanner with not many slices um very important i think to give instruction for shallow breathing um to the patients my own preference is if you have you know a 64 slice or something a higher capability machine uh might be um you know to try and target something at a normal end expiration or or expiration if you have um the ability to do timing because um then the lungs uh are relatively uh deflated compared to um the PET images which are acquired over many breathing cycles and and the heart is a little bit easier to fit into the ct silhouette all right so so thanks rob and james uh i think these are all very important points and i think it is while this is important for any hybrid imaging any PET imaging this is going to become an important issue for floperida as given its resolution so our techs need to give us good images sorry tim go ahead yeah so i suspect many of the viewers here are are in uh practices as opposed to major hospital systems and it's not unusual for interpreting practitioners to show up in the lab at 4 and 4 30 and the technologists have gone home and uh and you know i mean you you can't interpret these types of of studies uh it'd be foolhardy and you'll make mistakes uh and i i guess my question to rob and to james is uh can you kind of give a because i know there's lots of technologists on on the call here too uh can you can you have any words of sage advice to the technologists so that they don't pass this type of uh this type of misregistration on to the reading physician yeah um is it okay if i go first james go for it yeah in our center we actually use uh a color table that has uh kind of a stripe in it at about like 50 or 60 percent of the peak activity um and we kind of tell the text that you know that that 50 contour should be within the ct soft tissue um and that can help um you know to provide a kind of visual guide more a little bit more quantitative visual guide i know on some of the uh spect imaging stations they actually the vendors actually provide a contour around the pet activity and that can be helpful if there's um you know known activity um as you can see here as well so if you if you blend uh and just look maybe decrease the uh the blending there moaz you'll see that that white contour is is definitely outside in the lung right and so that can be kind of a helpful adjunct uh for the very helpful all right for the sake of time we're just going to continue to move on so i think one thing just to mention that the effects of misregistration may be more evident also with the tracer um just and so it's very very important to to do the quality control yeah okay yeah even if it's tough to do on your scanner you have to do it it's not like rubidium where it's it's more rubidium's more forgiving and on this one you really need to inspect it on every one and uh and be sure it's it's not if necessary it's been done all right marcelo uh you've been quiet so we're gonna ask you to help us with this case i was asked to interpret this case a few weeks ago this is from our lab 79 year old lady okay well thank you thank you moaz for giving me the easy case so uh so um okay uh so the images uh the the cavity uh at least on on first impact inspection here looks normal there's no no evidence of uh transient dilation of the uh of the lv um and what uh strikes me is uh you know first i started the apex and the apex seems to have a defect um and at least from my screen it looks like is uh somewhat reversible but then if i move beyond the lv apex into the apical section of the short axis images one can appreciate uh that there is a clear drop in the intensity of the uh of the signal when you compare for example to the base of the heart on the stress images uh if you can appreciate the intensity drops from base to apex um and you can see it there as well um and and that's not a normal uh that's not normal and you can see it at rest there is far less of a drop uh so so the drop in the signal indicates uh you know a gradient in flow right uh perfusion uh it seems to be reduced as we move away from the base of the heart and uh and it is reversible so i would say uh there's a medium-sized perfusion defect that involves all the apical segments on the apex and that it shows reversibility so now here you know the differential diagnosis for a tracer like this would be is this a flow limiting lesion or is this a patient that has just diffused disease uh that will give you this kind of gradient um and i would say most likely a flow limiting stenosis in the mid to distal led territory um but i have seen perfusion defects like this in people who have very severe diffuse disease with very narrowing and tapering of the lumen of the vessel as you go distally without focal disease uh but i would i would err on the side of flow limiting disease every time i see a case like this so just to uh like because we talked a lot about apical thinning uh is this like how for our audience those who are sorry yeah so i think here you know you can see for example in uh when you look at slice uh 33 or 31 you could see that there is reversibility in the apex right and and one thing we we mention is that you know apical thinning is typically a fixed abnormality that you see on the scan so when you see reversibility you cannot ignore it and then the other part of this is that you should not get totally fixated on the apex look at the adjacent segments as well and when you see that the apical short axis images are all abnormal you know it makes it you know very likely that the apex represents part of that abnormality and that you need to include it all right so quickly for the sake of time ejection fraction went up only two percent and you can see it's better at trust maybe compared to here yeah yeah this is not a case of high risk ischemia right like we saw on some of those proximal led lesions and so it's not surprising that the ef doesn't drop so from a quality standpoint this is a good quality and now we see these numbers so you can see the flow most led is like in the green so it's two and above but in the area of perfusion defect is below that if you look at the segmental numbers here you can see that the numbers are like 1.4 1 point a sudden drop from 2.2 let me zoom on it so you can see it very well so marcello can make his point about the gradients that you see here yeah so so you know what you're showing there um was is what we saw visually right that the flow the perfusion drops visually and so does the flow because we're measuring the same thing and so you can see the drop there um and the drop in the flow is like what you see in the cath lab with the drop in pressure when you cross a stenosis and and uh you know that would seem to me to be sort of a significant drop more than what you typically see in diffuse disease so so this will support the the you know the notion that this is likely flow limiting epicardial disease and this patient did go to the cath lab and she has an 80 percent distal led like in the area that's supplying this apical segment so clearly we just want to make sure that we talk about the apical thinning for floperidas so much but apical thinning should not be reversible when you see it reversible and you check your quality and you're sure about that i think that's going to be very helpful for you to make sure that this is ischemia i think this is a great case i think the other thing to mention is that that approach that marcello just described works mainly for the led right when you do that you have that step up does it i don't know that it works for the other no it works for the led it works for the led primarily but uh and so it's very helpful in a case like this um for other vessels there are different approaches but i think is you know it's beyond the few minutes that we have now to discuss that yeah all right we'll finish up with the teaser case that i was reading here so maybe we'll ask people to put in the chat what's the diagnosis here and you can put it in the q and a sorry q all right my apology all right prem what do you think or maybe you can also ask for help from them so this is a patient that has been having palpitations i had a lot of work up and came to us to evaluate had multiple echoes an angiogram and now i want to look at this so what do you see the first thing is you know we talked about the exquisite resolution and the papillary muscles and you know as you look at this particularly in the in the vertical long axis slices you see a very thick myocardium particularly close to the apex and this is quite a classic appearance of and i hope this is right quite a classic appearance of hypertrophic cardiomyopathy particularly the apical variety now in addition to that it does look like there is a little bit of a reduction a reversible reduction in perfusion in the apex and the adjacent segments and and that is interesting because you know there are there are a number of different possibilities here it could be obstructive disease but more likely it could be lvh and you know small vessel disease and just a supply demand type of mismatch so it'll be very interesting to see the rest of the data in this patient right so for the sake of time i'll show you the gated images which i agree with you the apex looks very full and maybe we can ask tim to walk us through these numbers how would he look at them from a flow standpoint quality is fine yeah so and as we talked about before on these high resolution images the apex always should look very thin compared to the rest of the myocardium it should never be thick it should never be thicker than the rest of the myocardium we talked about initial approaches to image interpretation it's one of the first things that i look at because you don't want to miss that so unfortunately so if we look at the flow numbers here the resting flow numbers look look fine when we look at the stress images or the stress flows they're down everywhere uh and uh the uh the ratios are also down um when we actually look at the maps if you want to bring those up so we can actually see what the numbers are inside the map yeah i'll give it to you one second yeah okay so interestingly yeah interestingly they're they're they're down uh everywhere even up towards the base of the heart in the on the peak stress uh numbers uh and uh so that's that's kind of interesting isn't that uh normally what we would see in in if it's isolated apical hokum is we would see the flow numbers down around the apical area and they look better towards the base of the heart and of course we we cannot differentiate between epicardial coronary disease and the flow abnormalities caused by the uh by the uh altered architecture from the hokum uh but um uh coronary calcium can be uh can be helpful in the right age group you know if you've got a 70 year old with no coronary calcium you might feel a little bit more certain that this is all hokum uh but in a younger person you you can't unravel this without coronary angiography the fact that the flows are down everywhere uh in this person would make me even more certain that we would have to do dependent on the coronary calcium you might be able to sort this out with coronary cta but most likely this would require coronary angiography so coronary angiography no obstructive disease and he's being worked up for apical hypertrophy i think there is some old data showing that with o15 water that you can get reduced flow in hypertrophic segment and in non-hypertrophic segment in hypertrophic cardiomyopathy so interestingly this patient had multiple studies before which they couldn't make that diagnosis but you can see here that apex so we focused a lot on the apex we kind of showed you thin apex reversible apex hypertrophic apex so i think the theme of the day is the apex and i just want to bring up this screenshot from the slides that benita just showed you so we kind of showed you all these variants where we showed you the myocardium well-defined thinner appearing we showed you the homogeneous uptake of the tracer we showed you the papillary muscle we covered the apical thinning and we showed you thin apex and reversible apex we highlighted the subdiaphragmatic activity rv we showed it to you at rest we also showed you the rv in ischemia where it becomes like even more intense uptake and finally we showed you the segmental brightening and exurgion on gated images so i think in the last minute i just want to thank all my panelists and my co-chair i want to thank ASNIC for the opportunity to present i want to thank our sponsor GE for their educational grant for their support of this program to run educational grant but GE it's primarily the content is from us and i want to thank also if you want this you can check the January webinar that we did and you will receive an email on how to receive the CME right after and benita if you want to say a closing word and we can close after yeah thank you to to you moaz all the hard work putting the cases together and to the panelists for really the excellent comments and participation and then to the attendees thank you for all the questions i'm so sorry i'm a terrible typist i couldn't type fast enough but thank you to everyone stay tuned for more education from ASNIC for as we implement the use of fluperidaz in our practice thank you very much everyone and have a good night thank you

American Society of Nuclear Cardiology

F-18 PET

fluperidaz

nuclear cardiology

cardiac perfusion tracers

Dr. Maaz Al-Mallah

Dr. Penita Shirentaitawi

image quality

coronary artery disease

radiopharmacy distribution

myocardial blood flow

motion correction

clinical implementation