Hello and welcome to this part of the virtual pet workshop, which consists of many of the didactic lectures that we used to do on in person, but of course, this isn't possible now. So my topic is to review the integration of coronary calcium quantification into the pet perfusion report. So here are my disclosures, none of which have any relevance to this topic. So the first thing is to remind ourselves that the PET scan provides us with a wealth of information for the evaluation of patients with ischemic heart disease. And this includes, of course, the presence of perfusion defects, which is the bread and butter of the perfusion PET scan, like for SPECT. Ejection fraction, of course, one difference here is that we may be able to assess ejection fraction both at rest and peak stress and look at the delta change in ejection fraction. The third element being the calcium score and the fourth element being the quantitative blood flow assessment, which we'll talk about in this presentation. Of course, coronary calcification has been around for many years, and because many of the devices that we use for PET imaging are hybrid devices, including SCT, it becomes natural that we would use the free information coming from the CT to be able to enhance our assessments of patients with not known coronary artery disease. Of course, one question is when and how to assess the extent of coronary calcifications, when is it relevant to do it? It is always relevant in patients without known coronary disease, and we'll talk more about that. Gated CT scans for a formal calcium score is recommended, but if you don't have the ability to obtain a gated cardiac CT, calcium score may also be assessed semi-quantitatively from the CT transmission scan, which will be obtained in every patient that comes for a PET CT. The interpretation of the calcium information requires that we integrate this into the rest of the information to try to make it for an actionable report. There's been work documenting the very good to excellent agreement between the formal Agatston score that we obtained with a gated cardiac CT and the semi-quantitative visual calcium score that we can obtain from a just non-gated CT transmission scan. This is one such study, included almost 500 patients from three centers, and exact agreement was in 63%, but 93% varied by no more than one category, indicating that it may have been minimal to mild or moderate to severe. Overall, there was excellent agreement between the formal gated cardiac CT and the transmission semi-quantitative score. Of course, why is that important? Number one is because we know that there is a relationship between the extent and the severity of coronary calcification and the likelihood of us finding obstructive coronary disease on angiography. This is early work from Dan Berman in 2004, documenting the relationship between the presence of ischemia, indicating an abnormal perfusion scan, and the likelihood that that patient will have a calcium score of over 400. You can see here the proportions of patients with ischemic studies indicating abnormal goes up with increasing calcium score here on the right-hand side of the slide. We're going to show you a series of patients to try to illustrate the possible clinical scenarios that we might find in these patients. First patient is a 59-year-old male with hypertension, dyslipidemia, diabetes, and obesity, who comes for a typical chest pain. The PET scan is shown here on the slide. You can see that there is no evidence of regional perfusion abnormalities. The ejection fraction in this patient at rest was 59%, and post-stress was 61%. And the encystolic volume did not change very much between rest and stress, which is essentially a normal finding on PET scans. The patient had no evidence of coronary artery calcium on the CT. And the blood flows that you can see here, both regional flows in each of the coronary territories, were essentially normal at rest. They rose normally with vasodilator stress, and the flow reserve was excellent, was around four in all coronary vascular territories and globally. So this is essentially a patient that had multiple risk factors for cardiometabolic disease, but had no evidence of calcium score, and the flows are normal. So in this patient, we will highlight in the report that the perfusion is normal, the ejection fraction is normal, there's no evidence of coronary calcification, and the myocardial blood flow and flow reserve are both normal. And then we will make a statement that this indicates a very low likelihood of obstructive coronary disease and identifies these patients at a very low clinical risk. We may want to say that there's no evidence of flow-limiting disease and no evidence of coronary microvascular disease. And both are important, particularly in patients who present with symptoms and have multiple risk factors for atherosclerosis, like in this individual. So this is a very comprehensive exam that essentially rules out the possibility that chest pain may be due to both either obstructive disease or microvascular disease. Here's another example of a 42-year-old male with obesity and hypertension who came in with atypical chest pain. His PET scan is shown here, essentially is a normal PET scan. It shows here at the apex a little bit of a reduction in tracer activity, which is typical for the apical thinning that will be associated with a little bit of partial volume effect and a reduction in tracer concentration. His post-stress LVEF was 49%, and the LV was mildly enlarged. His transmission scan, in this case, we did not have a gated CT, but you can examine here the transmission CT, showing essentially no evidence of coronary artery calcification on these images. Now, the blood flow quantification in this patient is slightly different than what we saw in the earlier case. In this case, flow at rest is normal. So normal flows are typically between 0.5 and 1.1, and that typically will depend on the patient's heart rate and blood pressure at rest, because blood flow at rest is essentially tied to oxygen demand, and heart rate and blood pressure will dictate that. So in this case, the patient has a very low resting blood flow, which is normal, probably related to beta blockers. Now, with peak stress, the flows rose about three times the baseline flow, but the absolute levels of peak flow was not normal, was reduced in this patient. And you can see that these flows are typically expected to be above a 1.8 or 2 mLs per minute per gram, and you can see that there's a homogeneous reduction in all coronary distributions, despite the fact that the flow reserve is normal. So this discrepancy between slightly abnormal stress flows and normal flow reserve are frequent encounters when we're reading PET scans, and how do we reconcile these findings? How do we know that this patient doesn't have evidence of obstructive coronary disease? Well, one way to do it is to examine the regional flows. This is a bullseye map with the regional stress flows for this individual, and what we look for is for gradients between the base of the heart and the distal part of the ventricle. We will ignore for a second the apex itself because of what we said, partial volume effects can really reduce flow artificially, but you can see that across any of the walls, there is no evidence of significant gradient between the base and the apical part of the ventricle, indicating that this is likely secondary to diffuse atherosclerosis and some microvascular dysfunction. In obstructive disease, what you will typically see is a gradient between the base of the heart and the distal part of the ventricle, and you can even estimate a fractional flow reserve by dividing the flows here in the apical part and the base of the heart to try to estimate the presence of flow-limiting disease, but in this case, no gradients. And so in this case, we would say that there's normal perfusion, borderline normal left ventricular function, however, the calcium score was zero. We would say that there was moderate reduction in the stress myocardial blood flow without a significant gradient from base to apex, and the flow reserve is normal. And this essentially is consistent with the presence of mild diffuse atherosclerosis and or microvascular dysfunction and identifies these patients at low clinical risk. The coronary flow reserve is the most powerful marker of prognosis that we have on PET scans. Here's another example of a 60-year-old female with hypertension, dyslipidemia, and diabetes who comes for evaluation of atypical chest pain. The PET scan shown here, again, mild reduction in the apical segment consistent with apical thinning, but overall, no presence of perfusion defects. Her ejection fraction at rest was 63 and rose to 66% without essentially enlargement or change in encystolic volume. Now, this patient did have extensive coronary calcifications that you can see here in the LAD, but there was also extensive calcifications in the other coronary arteries. So the question that we will ask ourselves is, is there significant, perhaps even balanced ischemia in this patient with multiple risk factors for coronary disease? So here, the flow information will become extremely relevant. And so when you go to the flows, you identify that this patient has essentially normal flows here around 0.8 mLs per minute per gram. They rise normally to slightly above 2 in most of the territories and the flow reserve essentially normal. So stress flows and flow reserve are concordantly normal in this individual with extensive coronary artery calcifications. So what we would highlight in the report is that there is normal, no evidence of regional perfusion defects. Ejection fraction is normal. It rises normally with stress. However, the calcium score was over 1600. And then we would say, despite the extensive calcifications, stress myocardial blood flow and flow reserve were appropriately normal in or concordantly normal in both regionally and globally. And that would indicate that this patient has extensive atherosclerosis as illustrated by the calcium score. But there is no evidence of either flow limiting disease or microvascular dysfunction. And this makes it for a very actionable report. Obviously, the reason we're emphasizing the calcium is because there's complementary risk stratification between calcium and perfusion imaging. And here are two examples that will illustrate that. These are two patients with symptoms and both have normal, essentially PET scans, indicating perhaps no evidence of regional or focal flow limiting disease. When we look at the PET scans, we would say the risk associated with the two are probably equally low. But when you examine the coronary calcium scan, you can see that the patient on the top has essentially no evidence of calcium, but the patient on the bottom has extensive coronary calcifications. And then the question is, do we still think that these two patients have the same equally low risk? And intuitively, one would say, no, the patient on the bottom probably has much higher risk of adverse events. And indeed, there's data both with SPECT and PET indicating particularly for patients with normal perfusion scans here in the light blue color, that despite the presence of a normal scan, extensive calcifications enhances the risk of annual events for both death and myocardial infarction. So it is pretty relevant information that is very actionable on the report. By integrating the two, you are able to essentially cut in half, when your flow reserve is normal, you're cutting in half the risk at any level of calcium information. And this is very relevant in light of the findings of the Scott Hart trial. As you know, the five-year outcomes show that the strategy of CTA first in the evaluation of patients with coronary disease was associated with a relative reduction, with a 40% relative reduction in the rate of myocardial infarction. And that has been attributed to the fact that when we see the plaque, we tend to act more aggressively on the management of risk factors and the management of preventive medication. So the calcium information in the PET scan will serve that particular purpose of being able to guide clinicians on how to more aggressively manage the patient's underlying coronary atherosclerosis. Here's another example of a patient who is 63 who has hypertension and presents with exertional dyspnea. This patient was evaluated first by the CT scan, and you can see that the patient has extensive plaque, both calcified and non-calcified here in the LAD as well as in the proximal circumflex coronary artery. However, the PET scan shows essentially no evidence of perfusion abnormalities, and the ejection fraction rose normally from 48% at rest to 63% post-rest with a concordant reduction in encystolic volume index, indicating at least no evidence of focal flow limiting disease. The perfusion information showed that there was, however, a slight reduction, again, a discordant slight reduction in stress flow with a normal flow reserve, and how do we deal with that? How do we know this patient doesn't have essentially obstructive coronary disease? Again, we look at the stress flows, and we see that the regional stress flows show minimal gradient here between the base of the heart and the distal part of the heart, indicating that this is all likely non-obstructive atherosclerosis or a result of combination of atherosclerosis and microvascular dysfunction. So this is how I think you're able to integrate the regional information into the global information to try to make sense and make an actionable report. So in this patient, we say there's normal myocardial perfusion and ejection fraction with a normal rise in ejection fraction. Calcium score was, you know, extremely high, and there was mildly reduced flow, both regionally and globally, without significant gradient from base to apex and normal flow reserve, indicating that this is the result of diffuse non-obstructive atherosclerosis. And this patient, of course, will be managed more aggressively for his lipids and other risk factor modifications. So in summary, we say that calcium information adds important information that helps with diagnosis, prognostication, and overall management of coronary disease. It should be a part of a routine PET-CT imaging exam in patients without known disease, either by obtaining a formal gated CT for formal calcium scoring or doing semi-quantitative assessment from the CT transmission scan. Quantitative flow offers important complementary information that becomes crucial to try to make sense out of the often discrepant information between calcium and the regional perfusion defects. And this may help us exclude obstructive disease, exclude microvascular disease, or guide us on diffuse non-obstructive disease to help guide, ultimately, diagnosis and patient management. Thank you very much for your attention.

coronary calcium quantification

PET perfusion reports

ischemic heart disease

calcium score

risk stratification

coronary atherosclerosis