Hello everyone, my name is Mouaz Mallah, I am the Director of Cardiovascular PET at Houston Methodist DeBakey Heart and Vascular Institute and today I would like to discuss with you a few cases related to my cardio-blood flow with rubidium perfusion imaging. I would like to acknowledge the contribution of Dr. Talal Nabilsi who is at the University of Kentucky and one of our prior trainees. These are my disclosures. Okay, so the learning objectives for this presentation is to describe steps to do quality control for blood flow data, I would like also to describe the findings from rubidium PET images to effectively use the myocardial blood flow in the management of these patients and also to see how we can use gated information effectively in the overall contribution of the imaging to the final diagnosis of these patients. For all these studies, these were done using pharmacologic vasodilator stress using regatenasone, we used rubidium 82 and our dose is between 10 to 20 millicuries because we are using a digital PET system, usually if you are in your practice you are using a non-digital scanner you need to use a higher dose of rubidium usually in the range of 30 to 40 millicuries. So let's start with the first case, the first patient is an 81 year old lady who had history of hypertension and dyslipidemia who was referred for the evaluation of chest pain. So here we see her images that are related, that were obtained using vasodilator stress, on top you see the stress images, the lower rows are the rest images, these are all CT attenuation corrected and you see normal perfusion imaging without evidence of perfusion defect. You can see the effect of the increase in the heart rate of the patient as the cavity gets smaller, but there is no evidence of myocardial perfusion imaging defects. Her EKG response was normal. We also do in our lab coronary artery calcium scoring on every patient that does not have known coronary disease and her calcium score turned out to be 2,941, so that is very elevated even in an 81 year old lady. When we look at the gated images you can see that her ventricle augments well, there are no regional worn motion abnormalities, her resting ejection fraction was 67% and increased by 6% with vasodilator stress to reach 73%. Let's go and look at the myocardial blood flow imaging and here you can see nice input function both at stress and rest and these are the myocardial time activity curves and there is nice uptake in the myocardium with rubidium. You can see her resting flow is elevated primarily due to elevation in her resting blood pressure, but as we go with the stress flow you can see that she increased her stress flow by almost 3 times and her reserve was a total of 3 globally across different, the global myocardial flow reserve was 3 which indicates that her flow increased 3 times after giving her regederosol. So how do we integrate all of this together? So we have a normal perfusion study, she has more than 5% augmentation with stress, however she has extensive coronary artery calcification which is known to have an adverse, which is associated with adverse outcome over long term, but this is kind of counter playing with a myocardial flow reserve more than 2 which suggests that she may not have obstructive coronary disease. So how do we put it together? The only adverse event here is extensive coronary calcification, because of that the referring physician elected to send the patient to coronary angiography and you see that there is no evidence of obstructive disease, there are mild non-obstructive disease in different segments, but there are no segments with obstructive disease given all what we saw before from the amount of calcium, they elected even to do invasive hemodynamics in the cath lab and the IFR was 0.96 in the right coronary artery and it was 1 in the LAD suggesting that there was no pressure gradient across her coronaries. So this is a case where you can clearly see that myocardial blood flow can help us identify the patients with low likelihood of obstructive coronary disease, obstructive coronary disease even in the setting of high calcium score and there were many other confirming findings including the normal perfusion, normal EKG as well as augmentation of the ejection fraction. So let's move on to the second case, the second patient is a 58-year-old lady who had history of moderate aortic stenosis and also referred for chest pain evaluation. So again looking at her perfusion imaging we can see that there is no definite perfusion defect, that stress again displayed on top or a stress displayed in the second row. The cavity appears to be a little bit bigger with the aortic stenosis with the stress and this may be related to aortic stenosis in this patient. You may appreciate that better on the black and white images where you can see the cavity a little bit bigger with stress but no perfusion defects. This is her baseline EKG and as we gave rigadenosine the EKG changes were exacerbated. So you can see here that the baseline is not normal, there are T wave inversions but as we gave rigadenosine now she has worsening T wave inversions in this case. We also did a calcium score, the calcium score is 19, sorry 119, when we did the ejection fraction we see that her resting ejection fraction was 79%, went up to 84% and here you can see the images there is almost the cavity not appearing. Now when we are looking at the flows and I can assure you that the quality of the curves were okay in this case, you can see that her resting flow was significantly elevated but her stress flow did augment a little bit but only to reach 101.37 and you can see this is like in all the areas here. So there is an increased resting flow significant partly due to blood pressure but also not completely explained by that and there is also significant, there is not a significant increase in her stress myocardial flow more than, so it's not reaching the 2 kind of margin. So to sum this case up we have normal perfusion, we have transient ischemic dilatation which is 1.26, in PET we are using 1.13, there are moderate coronary calcification and there are significantly elevated resting flow likely due to hyperdynamic state and outflow tract obstruction from aortic stenosis in this case. When we, this patient also went for an angiogram you can see that there is no obstructive disease, there is only this lesion here that you see in the LAD and in this patient actually in the LAD lesion you can see that it is not flow limiting which was confirmed on multiple views and this is the aortic stenosis on a CT scan which shows that she has actually progressed and this is her area of 0.7 cm2, so she progressed actually from moderate to technically severe aortic stenosis. So you can see here in this case the hallmark of what we see, multiple abnormalities but all related to the fact that the patient has aortic stenosis, she has transient ischemic dilatation, positive EKG, probably significant LVH on her echocardiogram as well as very high resting flow and inability to fully augment her, to augment her stress flow beyond what she is at to start with. So we're going to move on to the third case, this is a 60 year old male with a history of hypertension, dyslipidemia and obstructive sleep apnea who is being referred for evaluation of dyspnea. So again we're looking at the stress images on top and you have the lower images on the, the rest images on the second row and there appears to be a perfusion defect in the inferior wall going all the way from the apex to the base, it is a mild to moderate defect but it is there and you can see the difference between perfusion of the inferior wall between stress and rest. So always we look also at the other additional incendiary findings, this patient had very little if any calcium score, his coronary calcifications were only 17, he had normal EKG response to vasodilator stress and you can see his ejection fraction, his resting ejection fraction was 50%, went up to 54%, looking at it in terms of one motion abnormality there is not much other than just some global hypokinesis. Now looking at the flows you can see that his resting flow is normal in all three territories, his flow increased a little bit and specifically in the LAT almost three times, okay in the circumflex but there is not much increase in the RCA territory and in the area where we saw the perfusion defect the flow only increased by 1.5 times, so although his global myocardial flow reserve is normal there is some regional abnormalities that you see here. So looking at his fusion imaging and that should be part of every QC, so I want to overemphasize every patient that I've shown you, we do QC of their images and look at the emission transmission registration, we want to make sure that what we see is very normal and what we see here is that we see a normal perfusion and normal registration, so it's very important to look at that. You can see here that in this patient for example for specific the heart is kind of pushed downward so maybe part of that inferior defect may not be true and may be related to misregistration, the only way to prove that is to go ahead and ask the technologist to go back and process it and move the heart to where it should be a little bit higher and when the technologist did that now you can clearly see that that inferior perfusion defect has gone away and now we don't see that abnormality. So this is a normal study when the yeast were aligned the normal perfusion happened and there were no misregistration anymore and no perfusion defect, but also more importantly if you look at the myocardial blood flow now there is no perfusion defect, no abnormality in there, but his flow globally although now it's also improved and you can see all the other additional numbers including the RCA are in the normal range. So misregistration will also affect flow numbers and will result in abnormal flow, now this guy was in the good normal range so it's not as much affected, but if you are in the borderline range it may push you from normal, it may push the flow values from normal to abnormal. So to summarize this case we had abnormal perfusion and myocardial blood flow reserve primarily due to misregistration and when we reconstructed these images everything normalized including the blood flow data and including in addition to that the myocardial flow reserve. So usually misregistration is thought of to be more of an anterolateral defect, we wanted to show you one of another uncommon situation and that's why it's important always to check your fusion images and make sure that what you are calling is not a misregistration artifact and it's a troper fusion defect. So we're going to move on to the fourth case, this is a 74 year old male, he has history of end stage renal disease on hemodialysis, the patient is referred for ischemic evaluation due to elevated troponin on a recent admission. So we're looking at the rest of the fusion imaging, so as we do the rest and before we stress the patient we know that we are seeing poor counts and there is not much uptake in the myocardium, a lot of it is in the blood pool and this is in part due because we don't have enough counts of rubidium there despite having a digital PET scanner with high sensitivity. So we went back and looked at what is going on here, why we don't have enough counts and we again go back to the wider field of fusion images and what we can notice here is that there is a lot of blood pooling of rubidium up there and there is also another blood pooling of rubidium also in the SEC, in the superior vena cava coming into the right atrium. When we look at the blood flow for this patient, you can see that there is not much blood coming in at the right time, but also you can look at the quality of the input function. We don't have the nice rise and the nice coming down we saw in the prior cases. So this is a case where we have a poor input function, poor injection, and this may not be related to issues related to the patient, to the injection itself, the injector or others. This may be related to something else that this patient had pathologic and this is a non-diagnostic study due to pooling of rubidium in the left subclavian and this patient is a dialysis patient, he had multiple catheters in his left subclavian and he ended up actually with a tight stenosis in the left brachiocephalic vein. Now you can potentially think that you may want to try to re-inject the patient again from the right, but he had a fistula there and we could not be able to do that. So in these patients it's very important to look at the wider field of view and ensure that there is no, that the quality of the injection is very important and you have a nice input function as we saw in the prior cases. Okay, we're going to move on to the fifth case and this is a 65-year-old male, he's also known to have moderate lesion in the right coronary artery and LAD, coronary CT and geography, and he was referred for a skin-like evaluation. So looking at the images, these images look nice, there does not appear to be a very clear perfusion defect, so at least it's so far reassuring from the standpoint of the stenosis, so no ischemic defect in the inferior wall, no ischemic defect in the anterior wall and these were the two areas that were concerning. So as I told you, we're looking at the EKG also and there was no response, we are looking at the gated images and you can see that there is normal wall motion, nice contractility, his ejection fraction was at 57%, went up to 63% and there was no evidence of regional wall motion abnormalities. Now coming into the flow, now we can start to look at these numbers and you can clearly see that his resting flow is very nice and normal. This is what we expect to see, all segments in the normal flow, now we can see it's 0.62. Now the stress flow is very high and the reserve, I have to say that I have not seen yet in a clinical case as much of a reserve. There might be something going on and a few things that we would like to do, that we need to do to do QC is that first of all we check these dynamic images for motion and there was no motion, okay, in this case we want also to look at the input function and ensure that the rubidium injection is fine, no abnormal injection because of things related to the patient or related to the injection itself. So when we look at it now you can see that I see a nice input function in stress images, nice decay of rubidium, however I don't see that in the stress images, remember the stress flow was normal at rest, but very abnormal at stress and this is because I don't see an input function here. So what happened to the input function here? So the TECs were delayed in triggering the machine to start to capture the input function. It is extremely important that to get dynamic images you need to start the injection at the machine at a very close time so you can capture the input function. If you do not capture the input function then you end up in a situation like this where you cannot quantify the myocardial blood flow. So here we can quantify the myocardial blood flow at stress, but we are unable to quantify that at stress because we are missing that input function. So does that impact my perfusion imaging? No. So I can still see the input function here, sorry I can still see the stress images because anyway we don't take the first two minutes in these images. So these images are diagnostic, interpretable and they look normal. Ejection fraction, same story, it's not going to affect it, but the myocardial blood flow is highly affected and we cannot report it. This is not a diagnostic myocardial blood flow study. So you can see here normal perfusion, normal ejection fraction and these are not affected by the delayed trigger. However, the myocardial blood flow we cannot report it because we have an inaccurate stress and this is because of the delay in stress image acquisition. All right, one more case, looking at a 72-year-old female with a history of hypertension and hyperlipidemia who was referred for stress, for chest pain evaluation and we are looking at the perfusion images, again nice perfusion images, no perfusion defect here, the EKG response looks normal, her coronary artery custom score is 854, so that's also elevated for her age and we will see how we can gather additional information from the ejection fraction and looking at the contractility, it looks like it's contracting fine, there is no regional wall motion abnormality and looking at the rest ejection fraction, it was 54%, went up to 60%, again no regional wall motion abnormality, so so far everything appears to be normal with the exception of the calcium score. So she does have atherosclerosis, but she does not have stenosis. Her numbers also, her resting flow is relatively normal, her peak flow in terms of number also appears to be normal regionally and globally and they are almost equal across there. So what can we say about this? So when we go ahead and run the dynamic images, so you can see here that the dynamic images are much nicer in quality at the peak, while here you kind of get another, kind of a two peak situation. So if I move frame by frame, so now I see rubidium coming to the RV, coming to the LV and then disappearing, so it come and then start to disappear and then come back again. So we do have kind of more of a double peak kind of situation and this is something that we need to kind of study more, so let's look at the curve here. So the time activity curve, we saw the rubidium coming in, then it went down, then it went back up. We did not see that in the rest of the images, so I'm going to go back and run this again, so you'll appreciate that. So you kind of get a double peak, double gush of rubidium, first, now the second. So turn it again on the stress on top, you see the first coming in and then second, while in the rest it's only one peak and then it clears out. So what happens is that many of these patients, when they come in, sometimes the IV is anticubital and they bend their arm. So when they bend their arm, these patients actually, it's a rubidium kind of stick in the arm until it builds up pressure and then it moves out. So you don't see this nice input function again, and again, although the numbers are good and when we look at them, but again, this may not be that accurate because we don't have a nice time activity curve and input function. So it's very important to make sure that there was a good time activity curve and there was good injection so we can estimate how much rubidium is making it to the heart and then we can quantify how much made it to the myocardium and get a good estimation of the myocardial blood flow. So in this case, we have a normal perfusion, moderate or severe atherosclerosis in this case, but we cannot report the myocardial flow reserve, this is primarily in this case was related to the IV position in the arm which caused the kink, and then it's very important, I cannot emphasize that, like we emphasize looking at the fusion images is to ensure the quality of the time activity curves, make sure that you have nice injection, you have good time activity curve and input function to be sure that the numbers that you are getting from this dynamic imaging is accurate and has no problems in terms of reproducibility. And we'll finish up with the last case, which is a 74-year-old female, she had hysteria of hypertension, she is referred for preoperative evaluation, and again, normal perfusion, no evidence of perfusion defect, we're looking at her EKG response, she had normal EKG response, her coronary calcium score is more closer to the moderate range, her ejection fraction again is normal, so no regional one motion abnormality, her ejection fraction went up, so all in all I don't see any major abnormality, but when looking at the flows, now we're having a problem in the resting flow, so again, this is a state where the resting flow is extremely high, her blood pressure was normal, so how can we explain that? So we have a very high resting flow, very normal stress flow, and the reserve which is very low, but it's typically induced by, in this case, by a very high resting flow. The biggest question here is why is the resting flow high, is this real? I mean if the patient's blood pressure is 250 systolic at rest, then we may expect such numbers, but I can tell you we don't stress in our lab these patients, so this is not the case here. So let's make sure that this is not a technical issue. So the technical issues that we want to see is that first the input function, so in stress I see a nice input function, nice time activity curves, at stress, sorry at rest it's not the same, so what's going on here? Why the myocardium and the ventricular activity are like almost tracking each other here? So when we go back and look at it, so all the software will require that you put a tracker where in this software that we are using it has to be almost at the mitral plane, and you see in stress we have it in the appropriate place, but in rest it was placed partly over the myocardium, so that's why what we are measuring, we are telling the software this is the left ventricle is actually the myocardium. So thanks God this is an easy way to fix, so all what you need to do is to just go ahead and reposition that, so now we just kind of go ahead and pull this and put it where it should be, and then rerun our time activity curves, now you see the nice separation of the time input function here, you can see the input function, so good separation between myocardium and blood pool, and now when we look at our numbers, the resting numbers are normal, the stress numbers are elevated, and now we have a reserve which is in the range of almost 2.67, which is normal and goes along with our cases. So to sum it up, this is a case that was primarily because the tracker where we put our, where we defined our ventricle and blood pool was not in the appropriate position, and by repositioning it we were able to correct that abnormality in this case, and this can be done at the level of the software. So in summary, normal transfusion, normal MFR, and this one you can go ahead and correct it, and in this case the blood flow can be reported in this study and can be incorporated in the overall management of the patient. So in summary, I've shown you a few information here, we reviewed some cases, many of them were mostly low-risk scans, so the markers of low-risk scans include normal perfusion, more than 5% ejection fraction augmentation with stress, normal flow reserve, and absence of very low calcium score, and the presence of blood flow more than 2% as in our very first case, has very high negative predictive value to rule out obstructive disease as confirmed in this case by invasive hemodynamics, and now misregistration of the emission and transmission scans may result in perfusion artifacts, and misregistration typically results in an interlateral defect, and it's always important to check for fusion images to identify uncommon misregistration artifacts, and finally quality assurance of the dynamic images is very important to ensure that the numbers are correct at this looking at motion, and also looking at the different artifacts that we reviewed related to the input function. With this, I want to thank you for your attention, and thanks for joining us.

Cardiovascular PET

rubidium perfusion imaging

quality control

myocardial blood flow

obstructive disease

aortic stenosis

perfusion defects