Hello, everyone. My name is Dennis Calnon, and I'm a cardiologist in Columbus, Ohio, and it's my pleasure to talk to you about the clinical value of Cardiac PET. There is growing excitement in the nuclear cardiology community about all that PET offers for our patients, and I'm going to cover that today. I have no financial disclosures. We're going to talk about several factors in terms of the clinical value of Cardiac PET. We're going to talk about its unrivaled accuracy, its superior efficiency, the low radiation exposure, the unique information that's provided, including information about left ventricular ejection fraction reserve, as well as myocardial blood flow reserve, and coronary artery calcification, and then touch briefly on some of the applications beyond coronary artery disease, starting with the unrivaled accuracy. This slide shows some of the characteristics of Cardiac PET that set it apart. First of all, attenuation and scatter correction are performed routinely and are very robust with PET, leading to excellent image quality regardless of the patient's size and body habitus. The spatial resolution for PET is good with rubidium and excellent with ammonia. The difference in spatial resolution has to do with the differences in energy of the positron produced by these different radionuclides, which leads to differences in what's called the positron range. Myocardial tracer uptake is good with rubidium and excellent with ammonia. The timing of stress imaging is also an important factor. Rubidium images are acquired at peak stress, which gives us lots of extra information, which we'll talk about later. And with ammonia, they're acquired very early post-stress. Because of the robust attenuation correction, as well as the scatter correction and the high spatial resolution, this leads to superior specificity for Cardiac PET. And then on the other hand, there's also excellent myocardial tracer kinetics. If you compare the uptake of rubidium, which is an analog of thallium, its uptake properties in terms of its extraction fraction are higher than the technetium agents that we commonly use for SPECT imaging. Ammonia has an uptake that's even better. And flurpyridaz, which is a tracer that's in development, has extremely high extraction and the ability to track flow. The higher the myocardial extraction of the tracer, the more likely we are to detect milder coronary artery obstructive disease that may be flow limiting, but only slightly flow limiting. O15 water is also a PET tracer, although it doesn't produce clinically useful images, although it is used for myocardial blood flow assessment, and it is really considered the gold standard for this purpose. Because of the high myocardial extraction, as well as the ability to measure left ventricular function at peak stress, and the ability to measure absolute myocardial blood flow and myocardial blood flow reserve, this leads to superior sensitivity for Cardiac PET. So, if you compare Cardiac PET imaging to good quality SPECT imaging with ECG gating, as well as attenuation correction on the SPECT images, in this meta-analysis, you'll see that the pooled sensitivity for PET was higher at 90% compared to 85% for attenuation corrected SPECT, while at the same time, the specificity was also higher at 88% versus 85%. The ROC curve analysis in this study also showed that it was statistically significantly more accurate overall in terms of PET compared to attenuation corrected SPECT, and the important thing here is, many times in cardiology, we have to give up something in order to get something. For example, we choose one test because of its high specificity, knowing that we may sacrifice sensitivity, but when you choose to use PET, there's no need to sacrifice sensitivity or specificity. You get the best of both, and there's no trade-off required. The PACIFIC trial really highlighted the diagnostic accuracy of Cardiac PET compared to the gold standard of invasive coronary angiography with measurement of fractional flow reserve in each vessel, and in this study, the investigators found that Cardiac PET had the highest accuracy at 85% compared to the accuracy of SPECT at 77% and coronary CTA at 74%. So again, in this case, they used O15 water and myocardial blood flow measurements with PET, but PET turned out to be the most accurate when using the invasive fractional flow reserve as the gold standard, and because the test results are accurate, we also then become more confident in using the test results to guide patient management. This was a study performed by the investigators in Kansas City who looked at the referral for catheterization and performing revascularization depending on the results of pharmacologic stress imaging with SPECT and attenuation correction versus PET, and what they found is that patients with low-risk PET studies had a lower risk of referral for angiography and revascularization, and patients with high-risk PET studies had a higher rate of angiography and revascularization compared to those patients with attenuation-corrected SPECT. So what this means to me is that referring physicians know that the results of PET imaging are very accurate, and they feel confident making important management decisions based on the results. What about the efficiency of the testing? This is the PET-CT rubidium protocol we use in our laboratory at the present time, starting out with a topogram for positioning followed by an attenuation map CT scan. Rubidium resting images are acquired next, then regidenesan stress, and then peak stress images are acquired last. The procedure takes about 20 to 23 minutes in total to complete the study, which is extremely efficient. This allows for late-day add-ons to the laboratory in the late afternoon, which might save the patient an extra day in the hospital, or if testing is needed prior to surgery, this can be accomplished quickly, and this can lower overall cost of care for patients by doing it so rapidly. Because of the slightly longer half-life of ammonia, the protocol takes a little bit longer, but rest stress ammonia studies can also be performed in just a little more than one hour, so also very efficiently. What about the radiation exposure? This study looked at radiation exposure in a variety of labs across the country with SPECT imaging, with dual isotope imaging, and with PET imaging, and you can see here that in all of the studies with PET, the radiation exposure was quite low and well below the threshold of 9 millisieverts, which is what the American Society of Nuclear Cardiology recommends for our nuclear cardiology testing. And because of the short half-lives of rubidium and ammonia, there is very low radiation exposure to hospital staff or family members who are with the patient after they leave the stress lab and are near them throughout the rest of the day. There's really minimal to no radiation exposure for family, and that's another advantage. So when the American Society of Nuclear Cardiology put out its information statement on ways to reduce radiation exposure in myocardial perfusion imaging, they took this into account. The algorithm starts with, is the myocardial perfusion imaging study appropriate? Because obviously, if the test is not appropriate, then there's really no justification for any level of radiation exposure. But if there is an appropriate reason for the test and there's no comparable test available without radiation, then the next step is to consider, is PET available? And if it is, consider PET as first-line testing to lower the radiation exposure for your patient. It's also important to point out that PET was considered the safest stress imaging modality during the COVID-19 pandemic, especially during the early stages of the pandemic before vaccines were available and so forth. Some of the reasons for this, if you think about the guiding principles, pharmacologic stress is considered safer than exercise stress in terms of spreading viral infection due to the proposed increased likelihood of aerosolization of virus with exercise compared to pharmacologic stress. And nuclear imaging in general is considered safer than echocardiography because for exercise stress echocardiography in particular, the sonographer needs to be in very close proximity to the face-to-face with the patient to acquire post-stress images, whereas distancing is easier to be performed with nuclear imaging. So in our laboratory during COVID-19 pandemic, the order of safety was vasodilator stress PET was considered the best option because it's a shorter test duration, easier to distance from the patient. Vasodilator stress SPECT was sort of second choice option, dibutamine echo third, exercise SPECT fourth, and then exercise echo would be considered sort of the last choice, especially during the height of the COVID pandemic. What about the unique information that's provided? One of the important things is the left ventricular ejection fraction reserve, and that's because we acquire images, especially with rubidium during peak stress, and we're able to detect an increase in left ventricular ejection fraction and a decrease in left ventricular end systolic volume at peak stress compared to rest. The left ventricular ejection fraction reserve is defined as the peak stress left ventricular ejection fraction minus the resting ejection fraction. And the ejection fraction reserve correlates with the extent and severity of obstructive coronary artery disease. Importantly, in this study from Dr. Dorbala's group at the Brigham and Women's Hospital, a normal left ventricular ejection fraction reserve greater than increase of 5% at peak stress has a 97% negative predictive value for excluding left main or three vessel coronary artery disease. So this is extra information that can be very helpful when we're concerned about the potential for balanced ischemia or multivessel disease that might be underestimated. The ejection fraction reserve is very, very helpful for this purpose. The other area of unique information is myocardial blood flow reserve. And as far as I'm concerned, this is really the single most important thing that's provided with cardiac PET imaging, and it's really a game changer. This will be discussed much more, but I'm going to mention it at least a little bit in this lecture. It's important to remember that the coronary circulation is not just the macro circulation that's visible on invasive coronary angiography in the catheterization lab, which is what we mostly have focused on over the years, but there's the macro circulation and the micro circulation, which is important. By measuring myocardial blood flow and myocardial blood flow reserve with PET, we're able to integrate the hemodynamic effects of all of the things that contribute to myocardial tissue perfusion, including focal epicardial stenosis, which is what we mostly think about when we think about performing stress testing to determine whether people have obstructive coronary artery disease, but it also takes into account diffuse atherosclerosis, which is very commonly a cause for symptoms and ischemia, as well as microvascular disease. Myocardial blood flow reserve is the ratio of peak myocardial blood flow divided by resting myocardial blood flow. And this has enormous diagnostic, prognostic, and patient management implications, which we'll discuss. It's important to remember the interplay between coronary microvascular disease and epicardial atherosclerosis. This slide was taken from an excellent article from Drs. Takedi and DeCarli, which talked about the interplay between microvascular disease and atherosclerosis. And you can think about clinical risk as increasing as the extent and severity of obstructive coronary atherosclerosis increases, but also on the vertical axis as the severity of coronary microvascular disease increases. And there are important subgroups highlighted, such as in this red box, where patients that may only have non-obstructive coronary artery atherosclerosis in terms of the epicardial arteries, but yet they have severe coronary microvascular disease for a variety of reasons, which we'll discuss a bit more. And these patients also have a high risk for adverse cardiac events, even though they do not have obstructive coronary artery disease. This unique application of cardiac PET imaging and myocardial blood flow reserve was recognized in the recently published ACC AHA chest pain guideline. Figure 14 from the guideline describes a clinical decision pathway for ANOCA or ischemia with no obstructive coronary artery disease. Highlighting this side of the graph, looking at PET imaging and myocardial blood flow reserve measurement, you can see that we're able to really categorize patients according to those with no ischemia and normal myocardial blood flow reserve. These are people that have no evidence of microvascular disease or anything else, and they are really considered very low risk for cardiac events, whereas there are different subgroups of patients with abnormal findings, such as patients with normal myocardial blood flow reserve, but localized ischemia. These patients meet diagnostic criteria for ischemia with no obstructive coronary disease, but they do not have coronary microvascular disease. Patients with reduced myocardial blood flow reserve and ischemia have both, and patients with reduced myocardial blood flow reserve but no ischemia meet diagnostic criteria for coronary microvascular disease. It's important to remember that in all three of these subgroups of patients, they are at elevated risk for major adverse cardiac events, and this is why myocardial blood flow reserve measurements are so helpful. Myocardial blood flow reserve also allows us to detect multivessel coronary artery disease, in particular when myocardial blood flow reserve is normal, the likelihood of three-vessel coronary artery disease is extremely low, and myocardial blood flow reserve, as shown here in the ROC curves, is statistically significantly much more helpful than just some stress score looking at things in terms of relative perfusion. This study really highlighted the way that we can use myocardial blood flow reserve to exclude high-risk coronary artery disease in patients who have normal or only mildly abnormal perfusion images. The most important finding of this study is that in patients with normal myocardial blood flow reserve, in this case using a threshold of 1.93 or higher, patients had a 97% negative predictive value for excluding high-risk coronary artery disease. So when myocardial blood flow reserve is normal, it's extremely helpful in excluding high-risk coronary artery disease. The converse, though, is not true. When abnormal myocardial blood flow reserve is seen, this does not necessarily mean that the patient has high-risk obstructive coronary artery disease. An abnormal myocardial blood flow reserve only has a 15% positive predictive value for high-risk coronary artery disease, and there's two ways to look at that. One way to look at it is this means it doesn't work very well. We're not able to use this to detect multivessel coronary artery disease. The other way to look at it is that this still provides important information, and it still means the patient is high-risk and abnormal. And this is shown in multiple studies looking at the prognostic value of myocardial blood flow reserve. Here in this study, you can see that the lowest-risk group were those who had normal, some stress score, meaning normal relative perfusion, and also normal myocardial blood flow reserve. The highest-risk group were those who had abnormal perfusion based on some stress score and also abnormal myocardial blood flow reserve. But you can see that in patients with the same degree of some stress score, the added value of myocardial blood flow reserve, when it's abnormal, significantly increases the risk for cardiac events during follow-up. So, regardless of whether or not the patients have obstructive multivessel coronary artery disease, myocardial blood flow reserve, when it's abnormal, does suggest the patient has higher risk for cardiac events. This was also shown in a recently published very large study from Dr. Krishna Patel and the group in Kansas City. In more than 12,000 patients, they noticed that myocardial blood flow reserve added significant prognostic information to the overall population, as shown in the upper left. In patients with no ischemia based on relative perfusion in the upper right, patients with mild ischemia involving 1 to 10% of the left ventricular myocardium in the lower left, and those patients with more severe ischemia in the lower right involving more than 10% of the left ventricular myocardium. In all cases, the added value of myocardial blood flow reserve in terms of prognosis was very significant. In fact, the investigators were able to identify that for every 0.1 unit decrease in myocardial blood flow reserve, this was associated with a 9% greater hazard of death. So again, very important prognostic information from myocardial blood flow reserve. This study looked at the different sort of ways that you could think about myocardial blood flow in terms of stress myocardial blood flow versus myocardial blood flow reserve. Some might wonder if you can measure peak stress myocardial blood flow, why not do stress only cardiac PET imaging and just skip the resting image like we do commonly with SPECT imaging. And the reason why it was sort of highlighted in this study, and that is that the myocardial blood flow reserve has such important value. In this study, you can see that the annual cardiovascular mortality rate was highest in this red bar group or this left lower quadrant. Those are the patients who had abnormal peak stress myocardial blood flow and abnormal myocardial blood flow reserve. The lowest risk group, as you would expect, were those who had normal findings that peak stress myocardial blood flow and normal myocardial blood flow reserve. When you look at the two groups, the green group and the yellow quadrant, where they have discordant findings in terms of peak stress myocardial blood flow or myocardial blood flow reserve, you see that the higher risk were those patients who had preserved peak stress myocardial blood flow, but abnormal myocardial blood flow reserve. So again, it seems that myocardial blood flow reserve is the most important parameter when we're talking about predicting prognosis and cardiac death. The study from Dr. Patel and colleagues in Kansas City also were able to identify that myocardial blood flow reserve guides patient management. Here, they used a cutoff of 1.8 as a threshold for myocardial blood flow reserve, and they showed that patients with abnormal myocardial blood flow reserve did better with early revascularization than they did with medical therapy, whereas those patients with normal myocardial blood flow reserve did just as well or better with medical therapy. So again, survival benefit was seen from early revascularization in patients who had abnormal myocardial blood flow reserve. This is a case just to sort of illustrate some of the points that we're making about myocardial blood flow reserve. Here in this patient, you can see that there was very severe and extensive ischemia. You can see that there's an ischemic defect involving the inferior as well as the lateral wall, suggesting the presence of severe obstructive disease in the right coronary artery and left coronary artery or the left circumflex distributions. The transient ischemic dilation ratio was also elevated at 1.30. We use a cutoff threshold of 1.14 in our laboratory with our rubidium PET studies. The polar maps also demonstrate that there's very severe and extensive ischemia in the right coronary and circumflex territories with just a very small area of resting perfusion abnormality in this distribution. The LAD territory, based on relative perfusion, looks normal. And really, there's no way for us to tell, based on relative perfusion alone, whether the LAD territory is normal or mildly diseased or perhaps severely diseased as well. These are the gated PET images that were acquired. The resting ejection fraction was mildly reduced at 47%, and the peak stress ejection fraction declined slightly to 46%. That's an abnormal response. And in addition to that, the encystolic volume went up from 68 to 89 milliliters. These are high-risk markers. Now, again, here we could conclude that this may simply be because the patient has very severe two-vessel coronary artery disease in the RCA and circumflex territories. It still doesn't tell us with certainty whether the LAD territory is normal or also abnormal. So then we turn to the myocardial blood flow reserve information, and you can see in this case that myocardial blood flow reserve is severely reduced. The global myocardial blood flow reserve is 1.15, which is very, very severely reduced. The blood flow reserve in the circumflex coronary territory was 0.86. When the myocardial blood flow reserve is below 1, this means that it's likely that the patient is experiencing coronary steel, and usually this implies the presence of a totally occluded artery. The right coronary artery territory also had myocardial blood flow reserve below 1, but interestingly, look at the LAD territory. The myocardial blood flow reserve was 1.57, which is better than the other territories, which explains why the LAD territory looked normal on relative perfusion images, but yet the LAD territory has abnormal, moderately reduced myocardial blood flow reserve as well. This suggested to us that the patient likely has three-vessel coronary artery disease with less severe disease in the LAD distribution compared to the other distributions. So the patient was referred for coronary angiography without clopidogrel loading because we were suspicious that bypass surgery would be much more likely to be required than percutaneous coronary intervention, and in fact, the right coronary artery was totally occluded, which fit well with the myocardial blood flow reserve less than 1. The circumflex was actually a very small vessel, and the circumflex territory was largely supplied by a large ramus artery, which was also totally occluded, which fit with what we saw in the circumflex territory, and the LAD actually had 80% proximal stenosis, and again, remember, that's where the myocardial blood flow reserve was reduced modestly, and the left main had a mid-80% stenosis as well with some catheter damping on engagement of the left main, and the patient underwent bypass surgery. Because of the myocardial blood flow reserve information, we were able to predict that the LAD territory would also be compromised, and in fact, it was the case. This is another patient example where the relative perfusion images look quite normal. The TID here is normal at 1.00. The polar maps also demonstrate normal perfusion as stress and rest in the reversibility map. These are some stress scores and some rest scores and some different scores, which are normal, and then we turn to the gated images. Here, the left ventricular ejection fraction was normal under resting conditions at 66%, and it went up to 74% at peak stress. The encystolic volume also went down a little bit from 33 milliliters to 26 millimeters. This is a nice, normal response, which adds quite a bit of extra reassurance that the patient is extremely unlikely to have severe coronary artery disease. The left ventricular ejection fraction reserve is calculated at plus 8%, which is quite normal, and then the myocardial blood flow information provides us with additional reassurance that the patient is completely normal in every way. The global myocardial blood flow reserve was 2.46 with myocardial blood flow in each myocardial coronary distribution of above 2. Again, very, very, very reassuring. So, this just highlights how myocardial blood flow reserve allows us to answer many clinical questions. Some of our questions we have when patients are referred for PET myocardial perfusion imaging are, does the patient have obstructive coronary artery disease? In this case, we can be very confident at saying no. Does this patient have single vessel or multivessel disease? We can confidently answer that question as well. Would the patient benefit from revascularization? This patient clearly would not, given the fact that they have excellent myocardial blood flow reserve and normal left ventricular ejection fraction reserve as well. Does this patient have microvascular disease as the cause for their symptoms? No, we know that their myocardial blood flow reserve is completely normal, which really excludes microvascular disease as the cause for the patient's symptoms. And finally, and very importantly, did the patient respond to vasodilator stress? This is something that we really don't know when we just simply measure myocardial perfusion based on relative perfusion images. By measuring myocardial blood flow reserve, we're able to verify that the patient responded to vasodilator stress and that caffeine or other antagonists did not prevent them from responding. So, this again is extremely important information and it makes this test so valuable. While thinking about myocardial blood flow reserve and other clinical applications, this was an editorial that I wrote recently about an article published in the Journal of Nuclear Cardiology looking at one of the really best applications for myocardial blood flow reserve with PET, and that is cardiac allograft vasculopathy. This is a diagnosis that's really challenging to make based on invasive coronary angiography or any testing that requires relative changes in either perfusion or wall motion during stress, and that's because cardiac allograft vasculopathy is such a diffuse process involving the coronary vessels diffusely. Myocardial blood flow reserve is really ideally suited for assessing this entity and is really becoming the test of choice for following patients after heart transplantation. Coronary microvascular disease, this is really the non-invasive test of choice for this diagnosis as well, but there are other conditions like HF-PF, hypertrophic cardiomyopathy, amyloidosis, aortic stenosis, where there's emerging clinical applications for myocardial blood flow reserve. Take, for example, hypertrophic cardiomyopathy. There's evidence that myocardial blood flow reserve might be at some point used as an additional risk marker to identify patients who would benefit from defibrillator therapy. Again, it depends on how you want to look at it. Myocardial blood flow reserve is reduced in patients with severe hypertrophic cardiomyopathy, especially those with very severely increased left ventricular wall thickness. Some would say, well, this means myocardial blood flow reserve is not accurate in this patient population for assessing coronary artery disease, but I would argue the opposite and that myocardial blood flow reserve is very accurate at detecting the abnormalities in myocardial blood flow caused by the hypertrophic cardiomyopathy and the myocardial fibrosis and myocardial disarray leading to microvascular dysfunction. We should take advantage of the ability of myocardial blood flow reserve to assess these other types of cardiomyopathies and in terms of helping to guide therapy. HEF-PEF is another scenario where there's evidence from Dr. Tichetti and Dr. DiCarli's group to show that in patients who have abnormal elevation of the EDE prime ratio by tissue Doppler and also have abnormal myocardial blood flow reserve, these are the highest risk patients in terms of their likelihood of developing HEF-PEF over time. So again, the results are not necessarily predictive of the presence of obstructive coronary artery disease, but they add very significant prognostic information. Similarly, in amyloidosis, patients with cardiac amyloidosis sometimes have the most severely reduced myocardial blood flow reserve, as you can see in this example from the Brigham group where you can really visually see very prominent TID in this case caused by a very severely reduced diffuse subendocardial myocardial perfusion caused by cardiac amyloidosis. And you can see from Dr. Dorbala's research that these patients compared to those who have simply increased wall thickness from LVH from, for example, hypertension, patients with amyloid have very, very severely reduced myocardial blood flow reserve. So in the future, myocardial blood flow reserve might prove to be useful for detection of early stage cardiac amyloid and assistance selection of patients likely derive benefit from emerging medical therapies for amyloidosis. Similarly, in aortic stenosis, Dr. DeCarli's group with Dr. Zhao compared the ability of myocardial blood flow reserve compared to the ability of global longitudinal strain measurements to evaluate patients with asymptomatic aortic stenosis who are being considered for aortic valve intervention. And what they found is that among patients with normal global longitudinal strain, the risk of major adverse cardiac events was significantly higher for patients with abnormal myocardial blood flow reserve than those with normal myocardial blood flow reserve. So in the future, myocardial blood flow reserve might be used as a sensitive risk marker to identify patients with asymptomatic aortic stenosis who would benefit from earlier intervention, especially now as we're all entering the TAVR era. This is a practical guide for interpreting and reporting cardiac PET measurements and myocardial blood flow that was recently published by the American Society of Nuclear Cardiology and the Society of Nuclear Medicine and Molecular Imaging. I certainly recommend that you take advantage of this excellent resource, which really highlights many of the things that I've talked about and others will be talking about. In terms of unique information, if you perform your cardiac PET study on a PET-CT scanner, which is the way it's most commonly performed at the present time, we also can detect coronary artery calcification here in the left main and the LAD and the circumflex and in the right coronary artery. So this provides us additional information about subclinical coronary artery atherosclerosis, which by identifying this, we can alter the patient's preventive medical therapies and reduce the patient's risk for long-term cardiac events. Finally, applications beyond coronary artery disease. This was a meta-analysis of ways to look for myocardial viability and FDG PET imaging is still considered the gold standard for myocardial viability assessment. It's the most sensitive test compared to the other imaging modalities and it's truly the only modality capable of actually directly identifying the presence of hibernating myocardium. FDG PET is also very useful in cardiac sclerocardiosis. You'll hear more about this at this meeting for sure, but if you compare patients with normal findings to those with abnormal findings, there are a variety of patterns that can be seen. The most sort of specific one is when there's abnormal perfusion and increased FDG uptake in that same area. This can be a very useful sign of active cardiac sarcoid. And if you compare FDG PET to the alternative imaging modality for assessing cardiac sarcoidosis, which is cardiac MRI, you can see that both modalities are capable of detecting fibrosis and scar, cardiac MRI probably slightly even more sensitive for detecting fibrosis and scar than FDG PET. Both modalities can assess left ventricular ejection fraction and wall motion. But when then you start thinking about the ability to distinguish scar from active inflammation or the ability to assess response to therapy or the feasibility with severe renal failure, which represents at least a relative, if not absolute contraindication to gadolinium, as well as the feasibility in patients with all types of pacemakers and defibrillators, there are several advantages for FDG PET compared to cardiac MRI for evaluating these sarcoidosis patients. And finally, FDG PET has been shown to be helpful in evaluating for prosthetic valve endocarditis, as well as LVAD infections and pacemaker defibrillator infections. This is just one study from France that showed that moderate to intense FDG uptake was associated with worse outcome and new embolic events in patients with prosthetic valve endocarditis. So again, not just helpful for diagnosis, but also helpful for prognostic assessment and to help guide treatment. So looking at all this together and the impact that cardiac PET has on quality and value, if you think about the quality of what we provide with our cardiac imaging study as directly proportional to the diagnostic information that we get from this study and inversely proportional to the radiation dose required to get that information, you can see that by PET providing enormous amount of diagnostic information at a low radiation dose, this really represents very high quality nuclear cardiology imaging. And if you think about value as the quality of the study and inversely related to the cost, there is evidence to suggest that with cardiac PET, by avoiding unnecessary invasive coronary angiography and by avoiding unnecessary confirmatory layered diagnostic testing, and by maybe decreasing hospital length of stay due to the efficient protocols and so forth, that we can really have high quality at neutral or lower cost. And this represents an enormous increase in the value that we are providing to our patients. So with that, I will end and thank you so much for your attention.

Cardiac PET imaging

accuracy

efficiency

low radiation exposure

myocardial blood flow reserve

coronary artery disease

nuclear cardiology