Hello, my name is Mouaz Mellah. I'm the president of the American Society of Nuclear Cardiology. And my role today is to talk to you about the clinical value of hybrid imaging. These are my disclosures. All right, so why CT imaging and hybrid nuclear and CT imaging? Why do we need CT imaging to enhance the added, to have added value for nuclear imaging? And in this coming 20 minutes, I will try to show you the added clinical value of CT imaging and hybrid nuclear CT imaging. I just want to set the tone right. There have been other talks that you had about the different types of CTs that we do. The CT that I will be mostly focusing on is the low-dose CT, which is done for attenuation correction. And in the hybrid imaging document and prior physics lectures, this was very well characterized. This is a very low-dose CT, sometimes equivalent to three to four chest X-rays, PA and lateral in terms of radiation dose. And usually depicited, as you see here in the axial, we can look at soft tissue windows and we then take it and draw what we call an attenuation map, which is used for attenuation correction of these, of the nuclear images. The resolution of these attenuation maps are even lower than the CT attenuation correction. So why do we do that? First of all, we can calculate what we call a calcium score out of that. Now the calcium score CT is a little bit higher radiation dose. It is a gated CT. And in the guidelines, we put out why we do that and what is the added value of calcium scoring. And we will cover that in this lecture. But I just want to leave you here that coronary artery calcium score, which is done for assessment of patients with no known coronary disease is a gated CT scan and usually done with 120 kVP and usually reconstructed using three millimeters of slice thickness. And the value of this coronary artery calcium scoring is really to quantify the atherosclerotic plaque that we see here. It is a non-contrast study, does not require a heart rate reduction, and it allows us to quantify how much coronary calcifications are there using what we call the Agastone score. Now this CT is a little bit more higher in quality compared to the CT attenuation correction I was mentioning a little bit about before. And this one, you may be able to have higher resolution and better assessment of some incidental findings compared to the CT attenuation correction. So to summarize, what are the differences between the CT attenuation correction and calcium scoring? Usually the CT attenuation correction is a lower radiation dose. So it has a lower dose length product while the calcium scoring is a standardized protocol using 120 kVP. The CT attenuation correction is either acquired free breathing or end expiration, while the calcium scoring is a breath hold scan. The CT attenuation correction is not gated while the calcium score is a gated scan. And in terms of reconstruction, they're usually reconstructed at 2.5 to 3 mm slice thickness. So why do we need all these CTs? Either the CT attenuation correction or the calcium scoring? The first main difference is that our patients now are different in 2022 or even 2023. So you can look here that our patients have higher rate of obesity and obesity is going significantly higher by time. And this is data from the NIH and the CDC websites where you can see the amount of obesity has significantly increased over time. And this is even the severe obesity has significantly increased over time. On the other hand, you can see also that diabetes is also increasing in terms of prevalence, but also undiagnosed diabetes has been steady over time. And these patients, we need not only to look for perfusion defects in them, but also we need to know if they have atherosclerosis or not. So this is a very important finding that we need to know about these while doing myocardial perfusion imaging. So quantifying atherosclerotic burden in obese patients and diabetic patients is of utmost importance to allow for a full assessment of the patient risk, whether they have atherosclerosis or not, whether they have ischemia or not, and then to guide their medical management accordingly. So given the amount of obesity that we see nowadays, you can see here, for example, this is a non-attenuation scan that we're looking at the SPECT myocardial perfusion imaging without attenuation correction, and you can see a fixed defect that is there. Somebody might argue that there might be a slight reversibility or not. And when you go ahead and do attenuation correction for the same scan, now I'm pretty confident that there is no perfusion defect. So using attenuation correction, especially with CT, helps us reduce artifacts and enhance our specificity, thus eliminate the need for unnecessary resource utilization in the future. And then the guidelines that we published later on, and I will discuss later, we kind of summarize the evidence that we saw with this, and you can see that the sensitivity of myocardial perfusion imaging in these studies was about 80%, but by using attenuation correction, and this is for SPECT myocardial perfusion imaging, while using specificity has significantly increased from 68% to 83% using CT attenuation correction. So there's clear benefit of using this low-dose CT for the accurate assessment of these patients and to reduce unnecessary artifacts and unnecessary resource utilization. This is even more important among obese patients, as you see the main benefit of attenuation correction in this study by Dr. Thompson clearly shown that most of the benefit in attenuation correction was attained among patients with a BMI more than 30, where specificity was significantly reduced to 41% and significantly increased after that using attenuation correction. But I have to say that also patients that are lean with less than, with a BMI less than 30 also had some benefit from using attenuation correction. So we do recommend using attenuation correction across the board and not only among obese patients. There are certain times now with certain applications where using hybrid imaging allows us to localize tracer uptake. One of these applications is using PET myocardial perfusion, PET FDG imaging to look for endocarditis. I can show you this image and somebody might try to guess what is this image coming from? Where is this image coming from? We have literally very difficult, we are having difficulty to localize where this FDG uptake is. But when I show you a fused image with a hybrid CT, low dose CT and nuclear imaging, FDG imaging, now I can see that this uptake is around the aortic valve and there is very focal uptake and adjacent to the left and non-coronary, sorry, left and right coronary cusp in this patient. This is a patient who had surgically proven endocarditis which was diagnosed primarily by PET. You can see here that this is a very important aspect of allowing us to know where the uptake is coming from and allows us to be certain about the finding that we use to guide management. Another area that we are using hybrid imaging is needed to localize PYP uptake. And yes, we are recommending to do SPECT imaging with all PYP imaging. But more importantly now with using SPECT CT, you are able to localize where the PYP uptake is. Here you see, for example, some uptake in the bone and the vertebra, which is expected from a bone agent, but you can also see clearly some uptake in the septum and uptake in the posterior wall where it might be a little bit more challenging to see that without the use of CT imaging. Another helpful application of CT attenuation correction or CT use for localization is actually using FTG imaging in vasculitis. And here you can see that by using a CT image, we are able to localize where this FTG uptake is coming from. And this patient is coming from the ascending aorta and reaching out all the way to the arch. And again, we kind of covered it up. Sometimes we are able to localize endocarditis. And in this patient, there is big abscess. We are able to localize that this uptake is coming from exactly from the abscess where it is. I think one of the main applications of hybrid imaging nowadays, especially with using of attenuation correction and calcium scoring, is really allowing us to detect atherosclerosis. And I think in this day and age, every patient without known CAD was undergoing SPECT or PET myocardial perfusion imaging should have a calcium score done. And this is also now mentioned in the chest pain guidelines where it says for intermediate to high risk patients with stable chest pain and no known CAD undergoing stress testing, the addition of calcium scoring can be useful. And there are plenty of references that kind of highlighted that and I will cover some of them in this talk. But this is an approach that we have adopted and spearheaded over the years in our labs to be able to show that when a patient comes to the nuclear lab, we're not only assessing ischemia, but we are also assessing atherosclerosis. And there is so much added value in doing that. So again, what we are saying here that we're primarily using the calcium scoring to detect atherosclerosis. And here you see this diagnostic scan I kind of talked about in the beginning where we are able to detect coronary calcification, for example, in this patient in the left anterior descending artery. If we look at the CT attenuation correction, which is a lower quality CT, lower radiation dose in the same patient, I'm still able to see that coronary calcification in the LAD. Yes, the images are not of the same quality, lower quality, but it serves the purpose of helping us guide the detection of atherosclerosis, even on those low dose CT. Now somebody can say, well, in my practice setting, I'm unable to obtain coronary calcium scoring, dedicated scan, but I can do that attenuation correction. And there is still value in looking ahead in these scans and trying to make the diagnosis of atherosclerosis on the CT attenuation correction. This is a study that was done by Dr. Einstein and his group before where they looked at the coronary calcium score from the attenuation correction. And they came up with what they call the virtual calcium scoring compared to the Agastom score. And you can see here the agreement between the virtual calcium score and the Agastom score. You can see that most patients are within one to two groups. So most patients that were zero calcium score by virtual had actually zero calcium score by attenuation by the Agastom score somewhere in the one to nine and 10 to 99 smaller group. But at least you're somehow in the ballpark. You may be a little bit misclassifying the zeros, but those who have detectable calcium, most of it you are able to kind of come up with an assessment that whether they have mild, moderate or severe coronary atherosclerosis from this. So in this workshop, you will try to help you kind of gauge that and try to estimate how much calcium are there from this attenuation correction. Obviously, as you do more of these and you correlate with calcium scoring, you are able to guesstimate how much calcium and atherosclerotic burden is there from the low-dose attenuation correction scans and try to guide management of these patients, especially if they have normal perfusion scan, the presence of significant atherosclerosis should be a trigger for additional therapies for these patients, including aspirin and statin therapy. I'll try to show you here the added value of coronary calcium scoring. This is a patient who have a 73-year-old man who came in with chest pain and he had just an inferior attenuation defect, but no, like, profuse ischemic changes. But when we did the calcium score of the patient, you can see that there's ton of coronary calcification noted in the LED and also in the circumflex, less than the RCA. And when we calculated the calcium score, it was almost 1,700, and this patient has severe three-vessel disease. And this was not detected by the ischemic, by ischemia, mainly because the patient was ischemic in all three territories. And what we've shown in our group, led by Dr. Chang and Dr. Memerian, nearly now 14 years ago, that among those patients who have normal myocardial perfusion imaging, but have atherosclerosis, they have higher event rate, whether they have normal spec or abnormal spec. This is correct for total cardiac events, but also for all-cause death and myocardial infarction. So the point here is that coronary calcium score is adding on top of ischemic burden assessment, whether the patient has normal or abnormal myocardial perfusion imaging. And thus, it is very important to make that estimation or calculation of calcium score, whether you guesstimate it or estimate it among those patients, because it is very important to risk stratifying these patients. Even among PET myocardial perfusion imaging, there is data that is coming out to show that even among PET, with all its added value of better accuracy, flow assessment, you see all of these added value. When you look at those patients with coronary calcification, you can see that coronary calcification, when assessed by coronary calcium score, adds incremental value over ischemic perfusion defect in PET. This was shown recently in multiple studies. This is one study that I'm showing you here from the Cedars-Sinai group. This is another study that shows even incremental value over ischemia and myocardial blood flow. And you can see here that those patients who have, those patients who have significant atherosclerotic burden have worse outcome compared to those who have much less atherosclerotic burden, even among those who have normal perfusion and normal myocardial blood flow. So there is incremental added value of coronary calcification over ischemia and flow. So to put it all together, we need assessment of both atherosclerotic burden measured by calcium score, whether you do it from a calcium score scan or from an attenuation correction scan. We need ischemia assessment and we need myocardial blood flow assessment if you are doing PET. And this is our study that we published in Jack Imaging couple of years ago, where we looked at 4,000 consecutive patients with high prevalence of diabetes and hypertension. And what we've shown is that's very similar to the prior studies that were published later, that among those patients who have high calcium score, as the calcium score increase, the event rate increases, but also as the amount of ischemia increase, the event rate increases. So technically what you need is again, assessment of ischemia, assessment of atherosclerotic burden, as well as assessment of myocardial blood flow as you see here. So you can see also here, when we look at myocardial blood flow, that as a coronary calcium score increase, there is increased event rate, but also as the myocardial blood flow increase at every strata of coronary calcium, as the blood flow decreases, that there is increased event rate. So again, confirming the prior messages that we've been talking about, that even with PET, with all the added value of myocardial perfusion imaging, superior accuracy, higher myocardial, higher increased added value from myocardial blood flow assessment, we still see significant benefit from looking at atherosclerotic burden. So however, there is like, despite all the benefits that I've discussed with you so far, there is limited adoption of hybrid imaging in clinical setting. And that has triggered multiple investigations to try to understand why this is happening. And one of it is that there are some technical challenges. Technologists are concerned about some artifacts that they can do. They feel that there are some additional tools that they need to learn about to be able to do this very well. One of them is looking at misregistration. So for example, if these are not done carefully and the images are not well registered, you may end up with a perfusion defect in the lateral wall or the apex. And then by fixing attenuation correction, by fixing the misregistration, this is well done now, and you see that this is normal. So if you are going to go ahead and adopt myocardial perfusion imaging with attenuation correction in your practice, you have to be very careful about the side, about the accuracy of these, about the accuracy of these scans and be able to go ahead and make sure that you are able to do them very well. Another concern that has come up in practice is how to deal with the incidental findings. These incidental findings have been looked at on these attenuation correction scans in multiple studies. I'm going to show you a couple of studies here. This is one study looked at ammonia PET in almost 1,400 patients, and they report the dual incidental findings in nearly half of them, and 115 out of the 1,300, so less than 10%, about 8% were considered to be potentially clinically relevant in these patients. So these are very important to be able to recognize that, and this is a hallmark of this workshop that we will be discussing in these incidental findings. We also looked, for example, at this in our studies, and we've shown that we had a little bit higher per rate of incidental findings. So nearly 8% were new findings, and most common were pulmonary nodules, but we found 11 patients with new cancer diagnosis. So these are not minor findings and need to be able to recognize some and be able to diagnose some accuracy. So we know that there are challenges in addition to what I just described. The availability may be limited unless you have a machine in your lab, or you have some coordination to be able to do CT attenuation correction on a separate machine than the SPECT machine and then fuse these images via software. We know that we need to have technologists and physician training, as well as we need to have CT training for incidental findings. And again, this is a hallmark of this entire workshop, primarily focusing on these incidental findings. At this time, there is no separate reimbursement with SPECT-CT, but with PET, if you do PET versus PET-CT, the reimbursement is different. So SPECT, at this time, there is no difference between SPECT and SPECT-CT, but with PET, there is difference in terms of reimbursement between PET and PET-CT. And there are always some local challenges that need to be addressed, how to deal with reads, whether to use a separate CT machine to be able to generate these images, these are all very important. And that's why multiple professional societies came together, led by the American Society of Nuclear Cardiology, with the participation from Society of Nuclear Medicine and Molecular Imaging, Society of Cardiovascular Computed Demography, and the American Association of Physicists in Medicine, where we put together this comprehensive document of hybrid imaging, nuclear and CT imaging. And this is a document that was in the works for multiple years, which was a very comprehensive document, and I encourage you to go over this document, which is available from JLC and also from the ASNIC website, where we, in this document, discuss the hardware equipment consideration, whether you need to have a dedicated hybrid system versus separate CT and nuclear cardiology system. We discuss what's the minimum CT needed for attenuation correction and calcium scoring. All of these were addressed also in other lectures. We've discussed software considerations, technical performance, and what are the acquisition protocols for hybrid imaging. We also covered reimbursement and some challenges there. We also discussed some of the pitfalls, including misregistration, radiation exposure, and metal artifact, as well as the number of scans needed, as well as study interpretation and reporting. And we provide multiple schemes that can be used for reporting these scans, as well as what are the training considerations for the practicing physicians, as well as for physicians in training, and all by the board certification and eligibility of these physicians. So this is a very comprehensive document. I encourage you to go over it and familiarize yourself with the different protocols that have been suggested in this protocol, from acquisition to study interpretation and reporting, and finally for technical considerations. This is very important if you're planning to do hybrid imaging and get excellent results from this. So with this, I'm gonna stop here and I look forward to seeing you in the hybrid imaging workshop. Thank you.

hybrid imaging

CT imaging

nuclear imaging

calcium scoring CT

tracer uptake

atherosclerosis