Hi, my name is Ron Blankstein. It's my pleasure to welcome you to this webinar on Navigating PET Imaging. I hope you enjoyed all the lectures. I'm going to turn it over to our distinguished panel to introduce themselves. Hi, everyone. My name is Dennis Calnon. I'm a multi-modality cardiac imaging cardiologist in Columbus, Ohio at Riverside Hospital. Hi, I'm Sharmila Durbala. I'm the director of nuclear cardiology at Brigham and Women's Hospital in Boston. Hi, I'm Jamie Bork. I'm the medical director of nuclear cardiology and a multi-modality imager at the University of Virginia. Great. Well, thank you all. Dennis, Jamie, Sharmila, you all provided fantastic lectures. I personally learned a lot from watching your lectures and those of the other faculty, but we wanted to discuss some of the key points from the lectures. We all agree this is a very exciting time for PET and for nuclear cardiology. But despite that, the adoption of cardiac PET is probably a little slower than many of us would have expected. Dennis, what are some of the challenges for adoption? Why is the adoption a little slower than we would ideally like to see? Yeah. Even though there's a lot of excitement about cardiac PET in the nuclear cardiology community and it's growing steadily, there's still many hospitals, many large hospitals throughout the United States who do not have access to cardiac PET imaging at this time. And worldwide, there's very little cardiac PET performed in other countries around the world as well. So there's still a lot to be done. Some of the problems include the high cost of the tracers. And that's one of the biggest issues is the large expense upfront for strontium generators for rubidium or for ammonia cyclotrons to be on site. And that's a big obstacle. The other issue I think that's important is the lack of physician champions to push for cardiac PET at their hospital. Even though there's more fellows being trained now in cardiac PET than ever before, there's still many cardiology fellows who finish their training without any experience or access to cardiac PET. And they don't therefore have the confidence to go to their hospital administrators and their heart service line administrators and push for cardiac PET. And I think the lack of physician champions who are trained in cardiac PET and experience is one of the biggest obstacles. Others may have other comments. The other issue I just briefly would mention is that transitioning from SPECT to PET often involves transitioning from nuclear imaging with SPECT to hybrid imaging with PET CT. And sometimes that adds extra concerns about how to deal with the CT images. And that complicates things as well. So I think those are some of the main factors in my opinion. With high volumes of cancer imaging, it can be hard to get camera time. And in particular, prior to now the addition of flipiridaz, there's been no opportunity to have unit dosing. And so that has been difficult for labs to generate enough volume to justify a rubidium generator, even with some of the creative solutions in place. And that can make it hard to start a program. Yeah. And the last point I wanted to add was the technologist training. I think we do need more technologists who are comfortable and knowledgeable with cardiac PET imaging. Well, those are great answers by all of you. I'm going to turn to Sharmila next. Sharmila, you lead our nuclear cardiology lab at Brigham and Women's Hospital, where we have both SPECT and PET. And in the current era where PET has so many advantages, when should we think of referring patients to SPECT? Yeah, that's an excellent question, Ron. Just to go back in time, the Brigham and Women's Cardiac PET program was started in 2003, nearly 20 years ago. So when we started the program, initially we prioritized all of our pharmacologic stress patients and all of our obese patients and anyone with limited image quality on SPECT to undergo PET imaging. Now we are at an era where we can offer, in addition to vasodilator, exercise PET as well. So I think the current era of PET could extend into not just pharmacologic stress, but also exercise stress. And as you know, we use exercise PET with N13 ammonia in some of our pediatric patients, coronary anomalous cases, or cases where coronary compression is the suspected physiology for ischemia. And these are primarily the cases. But if you would have access to both exercise and pharmacologic PET, and you have unlimited time on the PET scanner, today I would venture to say maybe PET would be the way to go and perform all your patients as either vasodilator PET or exercise PET. So essentially, very few remaining indications for SPECT if you truly have the capacity to offer PET. I would mention for our audience, one downside of exercise PET is you don't get the information on blood flow reserve. So I know for my own patients, sometimes I've sent patients for both an exercise treadmill test and a PET, sometimes even on the same day, just so I can get information on both exercise and blood flow reserve. But let me turn to Dennis and Jamie. Are there any kind of compelling reasons why you would choose SPECT if a PET is available in your institution? I would agree that really if we have the opportunity to move as much as possible to PET imaging, I think that it is a superior functional test. I agree with you that exercise and all of the really powerful diagnostic and prognostic markers that come with it are really important. So I love your plan of doing an exercise stress on the same day that you do a pharmacologic PET. The one group, if you had to somehow balance between use of both, I would say patients who are able to achieve a high exercise workload may be less likely to have significant blood flow abnormalities. And so perhaps a SPECT approach could be used in those. But if you have access, I'd go PET as well. Yeah, I would agree. At our hospital where we have access to PET, we do much more PET, probably five times more PET than we do SPECT. However, in our health system, at the other 14 hospitals in our health system, it's all SPECT. And, you know, in my opinion, the times that I would respect, which I still do, are people who are capable of exercise, have body habitus that looks like the low likelihood of attenuation artifact and when my clinical question is more simple rather than complex. I'm not thinking about microvascular disease, for example. I don't need myocardial blood flow information necessarily. When the question is simple and those situations with good exercise capacity, I can do SPECT. But for the vast majority of patients, PET is preferable. Yeah, actually, I would like to add to Dennis's comment about coming back to PET, actually. When microvascular dysfunction is the question, obviously, vasodilator PET is the best of choice at this point. And we also use this for our cardiac transplant patients, preferably PET over SPECT. Yeah. It's a very, very clear consensus, I think, from all four of us that when PET is available, it's almost always, if not always, going to be the preferred test. All four of us are multimodality imagers that are involved in many modalities. And, of course, part of this discussion is when should you think of another test, for example, MRI, cardiac CT, stress echo. So let me turn to Jamie for some advice on how to think about this question in the context of other modalities. So I think it's fantastic that we are in an era where we have strong modalities that we could take advantage of the individual strengths and pursue a patient-centered imaging approach. So I really like a functional testing approach, and I like using PET in a lot of patients and SPECT, obviously, as we've discussed. But there are certain times, so patients who are younger and lower risk, where an anatomic approach, especially identifying the amount of non-calcified, identifying coronary artery disease can be important, and non-obstructive disease. And then on the other side, patients who have significant cardiomyopathies, a stress MRI approach can be beneficial. So I try to play to the individual strengths of the modalities. Great. So very important points. Let's talk about image quality. Image quality is so essential to everything we do, and, of course, PET, like any other device, performs the best when we have good image quality. I wanted to ask all three of you to share some of your tips for image quality when performing PET with our audience. Maybe I'll start with Sharmila. Yeah. Again, education, coaching, and training, right? For optimal image quality, we need to educate our technologists. They play the most important role, I think, along with the patient in obtaining excellent quality images. So we do need to coach the patient to breathe normally, to not move, things like that. And then, of course, make sure that the CT and the PET images, the emission and transmission images, are well-registered, well-oriented. So I think a lot of image quality in PET really boils down to these points, that you make sure the patient is cooperative and not moving during the scan. Now, image quality also depends on how much radiotracers are administered relative to the patient's body weight. And that, I think, we are now able to do better because we have weight-based algorithms, and the rubidium infusion pumps can be programmed to administer activity based on the patient's weight as well. So beyond that, I think attention to really the image quality at the time of scanned interpretation. So the main difference between SPECT and PET, obviously, we all know, is you're scanning during maximal hyperemia, for the most part, especially with vasodilator stress, you're scanning during maximal hyperemia. So therefore, patient is experiencing hyperemic effects and may have motion or breathing artifacts from that. With exercise SPECT, especially if you're using ammonia, patient motion is a problem because we scan soon after stopping exercise. There could be an upward creep artifact. So we would always say for ammonia, you stop the treadmill, let the patient settle down for two to three minutes in a standing or sitting position before laying them down in the PET scanner. Hopefully, with fluid period, that would be less of an issue because you can scan half an hour later, but then everything returns back to baseline. Okay. Dennis, Jamie, any other tips? Dr. Milla, obviously, it was a very comprehensive answer. So anything to add? Sure. I'll just add that it's important to remember that patient motion is really the critical one with cardiac PET. The attenuation artifacts are not really an issue if you do attenuation correction correctly, which we do. But patient motion is harder to detect with cardiac PET because you don't have the rotating raw images like you do with SPECT to look for patient motion because the images are acquired simultaneously rather than sequentially like they are with SPECT. And it's harder to correct with PET. It's becoming available, but not easy to do motion correction with PET, and the stakes are higher as well. As we mentioned with SPECT, you can acquire your image again if there's a lot of motion with PET because of the short half-life of the tracers, you've got your one chance. So that's why, you know, again, patient motion is even, in my opinion, even more critically important with PET than with SPECT. Yeah. So just to add to what Dennis said, absolutely, I fully agree. Think with fluid period as advantages, we may be moving more like a system, maybe acquisition. If the patient moves, we may have the opportunity to rescan the patient if we pick it up immediately. So things are going to be slightly different with fluid period as more similar to SPECT imaging in that sense. I would just highlight that I think it's important as labs move to starting PET to recognize that when physicians are interpreting the imaging studies, they need to recalibrate. With PET imaging, there's superior spatial resolution, and so there are patterns of thinning, for instance, at the apex that are just different from reading SPECT, and so it's important to recalibrate to the new modality. Great points. Any other points for interpretation of PET that we should share with our audience in terms of tips for how to interpret images? Obviously a big topic, Sharmilla, you gave a whole lecture on this, but any kind of key points for interpretation? I could get started, and others could add. Interpretation obviously relies heavily on systematic scan interpretation, as with SPECT. We just need to be very systematic, go step by step, make sure the image quality is adequate, there's no misregistration artifact, there's no patient motion before we start interpreting. Then, of course, we interpret the perfusion, polar plots, gated imaging, as well as myocardial blood flow. So it's important to look at the quality control for the blood flow images as well to make sure that the input function is adequate and that it is an interpretable image. So once we have all of that in place, I think interpretation becomes relatively straightforward. We interpret the relative perfusion images, we look at the polar plots, the ejection fraction, and remember with PET, we have rest and stress ejection fraction, and if the EF drops even with vasodilator stress, that is a bad prognostic sign, indicates multivessel or left main disease. Now with myocardial blood flow imaging, I think it adds a whole lot more of information that we can look at, including probably detection of balanced flow reduction in all territories versus excellent hyperemia in any given patient. And the one point that we have started to do more recently in terms of interpretation is if the blood flows have not augmented adequately, we are looking at the splenic switch-off phenomenon. So basically we go to the fusion screen, look at the counts in the spleen at rest in relation to the liver and compare that to the splenic counts in relation to the liver at stress. And typically, we expect the splenic counts to decrease with stress. So that's one new thing that we've added, I think, to our interpretation more recently. I think when we talk about interpretation, I think also recognizing artifact is always important for all of imaging. I see a word from one of you on ammonia-related artifacts from uptake in the lungs versus misregistration artifacts between the emission and transmission. Does anyone want to give a tip to our audience on that point? We use ammonia. And I do think the lateral wall artifacts can be very challenging. And so it's important to keep in mind that those can happen. I think as we're talking about, there are a variety of reasons that those can happen. For misregistration artifacts, I think are particularly challenging for folks who aren't coming from a SPECT-CT background where they have to really make sure that the images are lining up appropriately. So I think that's an important first step in training when starting a program. I'll just mention my own experiences that misregistration artifacts used to happen much more when this was a manual process. And now that it's automatic, the software, at least our software, has improved a lot. So it's still very important to look for it. But the rate of that is much less common. And then I guess for ammonia, the other artifact I was getting at was when there are pleural effusions, there can be uptake of ammonia by the pleural effusions. And sometimes you can normalize to the kind of hot areas in the lungs. So just something else to look out for. I think it's a reason why if someone's in heart failure, I think there's probably other reasons, but if someone is in active heart failure, it's usually not a bad idea to diarrhea some first before the PET, especially if you use ammonia. Yeah, lung uptake is a problem, particularly in patients with heart failure. And intense lung uptake can interfere with interpretation of the perfusion images, particularly the lateral wall, which is right next to the lung parenchyma. And we also see that for some unclear reason in smokers. People who smoke can have intense lung uptake with ammonia. So smoking and low ejection fraction with heart failure are the three reasons for intense lung uptake. I was just going to say, going back to Sharmila's initial response, which of course was excellent and comprehensive, I think it is important that with all of the different elements that we get on a cardiac PET scan, that we make sure that we provide a reconciled interpretation that incorporates both the relative perfusion and absolute myocardial blood flow, and then also very specifically that we incorporate some kind of assessment of the non-obstructive coronary disease that we see on the CT. Absolutely. That's exactly the topic I actually wanted us to talk about next. So maybe we'll talk about, I'll ask Dennis, how do you report a study when you have a perfusion defect, a visible perfusion defect, and then you see abnormal blood flow reserve in the same distribution? Or if you see abnormal reserve in all three distributions, how would your interpretation be different in those two cases? Yeah, it's one of the major advantages of cardiac PET is the ability to really confidently identify single-vessel disease, two-vessel disease, or three-vessel disease using both the relative perfusion images and the defect, as well as the myocardial blood flow information. So I find it very helpful when you see, for example, like you described, a single-vessel ischemic perfusion defect with reduced regional blood flow reserve in that region, but completely normal myocardial blood flow reserve in the other two areas. You can confidently predict that the patient has single-vessel disease, and you know that they're likely to receive PCI if they have symptoms that warrant catheterization. And you know they're very unlikely going to need bypass surgery or have multi-vessel disease, and you can predict that with confidence. And similarly, when they do have a single-vessel ischemia, but they have very abnormal blood flow reserve in the normal appearing areas on the perfusion images, and they have extensive coronary calcification, you can be pretty sure they're going to end up having multi-vessel coronary artery disease. And for example, when we send those patients for invasive coronary angiography, I don't load them with clopidogrel like I would other people in anticipation of stenting, because I think they're likely to have bypass surgery, and so I don't load them and delay the bypass surgery by you know loading with clopidogrel. So that's something that we really can't do with just relative perfusion imaging, which is what's done most commonly with SPECT, and a major advantage of cardiac path. DR. SALGO Great points. Sharmila, on that focus of putting it all together, when you have patients who are referred for evaluation of microvascular disease, what do you focus on, the peak perfusion, the blood flow reserve, you integrate the calcium score information in there, how do we make that diagnosis? I feel like it's not always an easy answer on that one. DR. SHARMILA PANDYA Right. It's not easy, and microvascular dysfunction is increasingly becoming more common. I guess people are recognizing it more, and patients are being referred for that more often than before. So yes, absolutely. So the advantage of PET is we can look at microderm blood flow regionally as well as globally, and we look at it in relation to the perfusion images. If the perfusion images are completely normal and the flow is reduced globally and regionally, then the differential includes, is this microvascular dysfunction? Is this true balanced flow reduction in all territories from abstract to coronary disease, which is very unlikely with normal perfusion, but still a possibility? And of course, the third possibility is this submaximal hyperemia. So before we label it as microvascular dysfunction, I think it's important to exclude the other two possibilities. So we are looking at the splenic switch-off, and if we see a splenic switch-off, then we are convinced that this is real. And if it is real and you see lowered flows in all territories and globally, then the question becomes, is this microvascular dysfunction or is this balanced flow reduction? So we look at the calcium score, as you said, that could kind of lean one way and take us one way or the other. And then if there are other findings, a drop in blood pressure, sorry, a drop in ejection fraction with vasodilator stress, so we could look at other parameters that may tell us that this is more likely to be abstract to coronary disease. But the bottom line, I think, for our audience is there's no cutoff blood flow or blood flow reserve that tells you definitively that this is microvascular dysfunction and not obstructive epicardial coronary disease. So typically, in most of these cases, I would suggest some sort of correlation with coronary anatomy. And if the calcium score is low, I usually recommend starting with a CT coronary angiogram. And more recently, as we've discussed in some cases with the newer CT technology, maybe even with some degree of calcium, we could go ahead and still do a CT coronary angiogram. But in other cases where the symptoms are suggestive of ischemic disease or if there's extensive calcium whatnot, then an invasive angiogram could be considered as well. But what about, I guess, the other entity that falls under is this diffuse atherosclerosis patients who just have diffuse plaque. It's not obstructive. I guess maybe we can use, Pat, to look for ANOCA ischemia in the absence of obstructive disease. Or maybe this is all a continuum with microvascular disease, too, because by the time you have a lot of epicardial disease, you very likely may have some microvascular disease. How has PET been helpful in these patients with just diffuse non-obstructive plaque? Maybe I'll ask Jamie how you use PET in these scenarios. Well, we know that for patients who have reduced myocardial flow reserve and ongoing chest pain, they have a very poor functional status and impaired quality of life. And so I think identifying that population is really important to aggressive — well, for two reasons. One, to give them an answer for why they're having chest pain. And that can be very empowering for patients to receive a diagnosis. The other is to aggressively go after ischemia. And we're still sorting out the optimal therapies, but for now, sort of following our typical anti-ischemic approach, as well as aggressive risk factor reduction. And when patients have that much established atherosclerosis, being very aggressive and quickly moving to things like PCSK9 inhibitors can be helpful. Great. No, I think that's a really important point. We've learned that these patients definitely have a higher risk and require aggressive management. I will add that the flip side is also true of this, that sometimes we have patients with very high calcium scores. We're all asked to see them. And of course, if they're asymptomatic, we don't always need to do testing. But when they have scores over 1,000 and perhaps questions on symptoms, PEP can be very helpful in those cases, especially if the blood flow reserve is normal. It can be very reassuring. I think it's probably the only type of stress test that is reassuring in someone who has a really high calcium score. But Dennis, have you found that in your practice or those common patients, these really high calcium score patients? Yeah, sometimes. And it can be challenging because many of our patients don't nicely fit into just one category. They may have obstructive coronary artery disease and we treat it, but they also have diffuse epicardial atherosclerosis and they have to some degree, microvascular dysfunction related to their hypertension and diabetes and other things. So this is where PEP can be very helpful in sorting it out where patients are more complex than ever because we're recognizing these new entities, the diffuse atherosclerosis and the microvascular disease as well as their obstructive disease. So it helps to explain why some patients, you know, with typical angina and they have obstructive disease and we stent them and now everything's open, but they still have symptoms and now we can explain some of that a little bit better by the other diseases that we can uncover with the myocardial blood flow information. Yeah, no, those are great points, Dennis, and I really like your point that, you know, we often see overlap in a lot of these entities, you know, in webinars like this, we think of them sometimes in silos, but that's probably a lot less common than I think. It would be nice, right? It would be nice if they were all just one thing and not more than one thing, but. Yeah, it would be easier, I think. It would be easier. It'll be easier. Yeah. Well, let's talk about floor period. There's definitely some exciting opportunities ahead, and I'm curious to hear from all three of you how this may change the practice of PET in terms of both access and other opportunities for the field of cardiac PET. Maybe I'll start with Sharmila. Yeah, really exciting news. We have a novel radiotracer for PEC perfusion imaging and a novel radiotracer period. We've not had a new tracer in a while now, so very exciting times. So floor period, because of its long half-life of 109 minutes, really can be transported to sites that don't have a cyclotron as a unit dose. So this democratizes, as someone has put it, PET. People who don't have a cyclotron, who don't really put in capital investment for a generator, who don't have the volume needed for a generator, can now start ordering PET. So PET becomes much more widely available. And then, because of the long half-life, as I indicated earlier, this opens up the possibility of going all PET for myocardial perfusion imaging, really, really exciting times. Jamie? One of the advantages with that longer half-life is an increased ability to do exercise PET where, while it's been possible with ammonia, is a little more challenging, and so we can definitely do exercise PET. I think one of the challenges is going to be determining when to do exercise PET versus getting the absolute myocardial blood flow. Some of the aspects that may help with that include what the patient's anticipated cardiac workload may be. I think that might move you more towards an exercise approach. I think as we gain familiarity with this tracer, we may develop combined protocols where we do exercise and pharmacologic, and there may be even ways to get myocardial blood flow using exercise. I think people will be creative, and we'll see changes, but I think it's very exciting to have an additional option on the market. As Sharmila says, it's going to be really helpful for groups that previously have been completely unable to start a program. Yeah, I totally agree. I think this is exciting for patient access to cardiac PET, and I think not only to the majority of hospitals in the U.S. that don't offer cardiac PET, but around the world as well, I think this can really be helpful in getting access to patients worldwide with cardiac PET and to take advantage of the excellent image quality and so forth. And as Jamie kind of hinted early on, many hospitals have PET cameras used for oncology or other reasons, and floperidaz with unit dosing could really help, you know, you can just, you know, squeeze in one or two patients a day with floperidaz and use it as part of, you know, the PET camera that's already there, and you don't have to have the high expense of the generator or the, you know, on-site cyclotron. So I think that's where it's going to make a difference is getting hospitals started with cardiac PET that have never done cardiac PET previously. Great. Well, really important points by all three of you. I think I'm going to wrap up by stating that it's very clear to all of us that PET is really preferred over SPECT. This is, of course, something that was stated in the ACC chest pain guideline, but the challenge is still availability. It's not available everywhere, and I think floperidaz, one of the exciting things is helping make PET more available across more centers. It's a test that's not only is more accurate, but it also allows us to make diagnoses that we're simply unable to make with SPECT, ranging from, we talked about microvascular disease or ischemia in the absence of obstructive disease, I think also something that we can diagnose better with PET. But at the end of the day, a test that is more accurate for a patient, has better patient outcomes, has lower radiation, so we are all very excited about it in the cardiology community, in the imaging community, and, of course, in the nuclear cardiology community. So I will thank Dennis, Jamie, and Sharmila for joining me for this wonderful webinar. And again, we hope you enjoy the rest of the lectures if you have not yet listened to them.

PET imaging

nuclear cardiology

radiotracers

microvascular disease

floperidaz

technologist training

cardiac care