Hello everyone, my name is Talal El-Nabulsi, and in a couple of weeks I'll be starting my new faculty position at the University of Kentucky. I had the pleasure of training and working with Dr. Muaz Zalmallah, and together we put together a series of cases here regarding rubidium myocardial perfusion PET imaging, and hopefully we'll go through them together and you'll find them very helpful and informative. Nothing to disclose pertinent to today's lecture, and the learning objectives are as follows. So the scan parameters, just for consistency, we used regadenosone as our stress agent, our isotope was rubidium-82, and the dose typically used in our population is 10 to 20 millicuries because we have 3D digital PET scanners. So case one, this is a 48-year-old female with a BMI of 32 who was referred for evaluation of chest pain. These are her images, again just for orientation, stress on top, rest on the bottom. I'll give you guys a few seconds to go through it, but essentially you have homogenous myocardial uptake throughout on both rest and stress images. As you go more towards the base, this is the membranous septum with decreased count as expected both on rest and stress, but essentially we describe this as a normal image basically. As part of our PET protocols, obviously we have EKG response to the regadenosone, in this case the patient's response was normal, and coronary artery calcium score is also performed in all patients with no established history of coronary artery disease, and in this patient the calcium score is zero. We have the gated images over here, rest LVF and stress LVF as indicated here, so 67% at rest increased to 73%. This is a greater than 5% increase which is considered normal and a good prognostic indicator. Myocardial blood flow analysis is also performed on all patients undergoing PET imaging at the Houston Methodist. Pay attention to the resting myocardial blood flow here in each individual coronary artery territory which is normal, and during stress this is normal augmentation, usually two to three times the resting flow, sometimes a little bit higher as in this case, and the myocardial flow reserve, the total is 3.8 which is normal and a good prognostic sign. So in summary, this is a normal perfusion scan and the patient has many excellent prognostic markers including a greater than 5% ejection fraction augmentation with stress, calcium score of zero, and a myocardial flow reserve greater than two. So we can label this patient as immortal. Case two, so this is an 88-year-old male with a history of hypertension and a prior stent in his right coronary artery who was referred for evaluation of chest pain. These are his PET perfusion images. So as you guys can appreciate, there is a medium-sized moderate intensity predominantly fixed perfusion defect in the basal and mid-inferior and infralateral segments, again no reversible, no appreciable reversibility. The patient's EKG response in this case was nonspecific, the resting ejection fraction was 40% and with stress increased to 44%, and you may appreciate on these CINI images that there is hypokinesis of the inferior and infralateral myocardial segments, i.e. the same segments that had a resting fixed perfusion defect. Myocardial blood flow analysis in this case showed a normal resting myocardial blood flow and significantly reduced peak stress blood flow analysis in all coronary territories and the reserve that's also significantly reduced at 1.3. The software highlights the area of perfusion defect and also highlights the myocardial flow reserve within that area of perfusion defect and in this case is also reduced at 1.4. This is not only a poor prognostic marker for the patient but it may represent involvement of multiple coronary territories or severe endothelial dysfunction in the setting of known coronary artery disease and prior revascularization. In summary, the study was interpreted as abnormal with fixed defects in the RCA or circumflex vascular territories, there was hypokinesis in the area of perfusion defect, and the patient had several adverse prognostic markers such as a reduced baseline ejection fraction and a significantly reduced global myocardial flow reserve, which could, as I said, either represent multi-vessel involvement or severe endothelial dysfunction. And this was the cath report which showed non-obstructive disease in the previously stented RCA and moderate to severe obstructive disease in the circumflex and OM1 or ramus branch and also in the LAD as well. The patient underwent revascularization of the significant stenosis and was treated medically as well. So moving on to case number three, this is a 73-year-old female with a history of type 2 diabetes and hyperlipidemia who was referred for preoperative risk assessment prior to abdominal surgery. These are the rest and stress perfusion images, I'll give you guys a second to take a look at them. So this one is a little bit more tricky, maybe more subtle in terms of perfusion defects, but if you focus on the apical anterior and apical cap, you can see a reduction in counts. Very mild, small area of reduced perfusion in the stress images. However, some of you may have noticed that the RV uptake is more prominent on the stress compared to the rest, and the cavity in stress is also dilated significantly compared to the rest. It's consistent with transient ischemic dilation. And it may be easier to appreciate on the gray scale here, so stress significantly dilated compared to rest. Resting EKG, poor RV progression, left axis deviation, normal sinus rhythm, no resting STT abnormalities of note. However, during peak stress, notable up to two and a half millimeter ST depressions in the lateral leads and probably some mild ST elevation in AVR and frequent PVCs as well. The calcium score was severe, greater than 1,000, and the LVEF went from 70% at rest all the way to 50% during stress. So global hypokinesis with stress. This is the myocardial blood flow analysis. As you can see here, the resting myocardial blood flow is a little bit above the, what we expect to be normal, which is typically anywhere from 0.8 to 1, sometimes even 1.2. We struggled to understand this. The one possible explanation is that this patient has severe and macrovascular disease and severe stenosis in all coronary territories that the vessels are maximally dilated. So maybe that's the required blood flow to maintain homeostasis or good perfusion to the myocardium at rest. As you can see during stress, there is almost no augmentation of the flow and a reserve of 1.1, and this is diffused across all territories. So again, very poor prognostic marker, but also in terms of diagnosis, very suggestive of multivessel disease. So the study was interpreted as abnormal with a small reversible defect on perfusion images, global hypokinesis with stress and a significant reduction of the LVEF and a TID ratio of 1.31. Of note, we use a cutoff of 1.13 on the rubidium PET regadenosome images. And the adverse prognostic markers, as we alluded to earlier, is an MFR of 1.1 and significant reduction of LVEF with stress. So putting everything together, you expect this patient to have multivessel disease. And this is in fact what we found on the cath images. The patient had diffused disease in the RCA with an occluded distal segment and PL branch. And then you can appreciate the tight, severe stenosis in the distal left main as well. So the patient was referred for coronary artery bypass surgery, and she did well afterwards. And obviously, the abdominal surgery had to be postponed until afterwards. So case four, this is a 62-year-old female with a history of lepto-diabetes and hypertension referred for accelerating chest pain. And in the emergency department, her biomarkers were negative. These are her perfusion images. So you can appreciate mild to moderate perfusion abnormality in the basal anterior and anterior septum during stress, completely normal during rest images, and moderate, even severe intensity as you go towards the apical segments. So it's quite sizable. It's a large perfusion defect. And the EKG response was nonspecific, and the coronary artery calcium score is zero. So this is a moment where we should pause. Again, it's not impossible or out of the ordinary to find perfusion defects in patients with a calcium score of zero. However, this is something that you always have to double check. Make sure that the images have been aligned. There's no misregistration artifact, because that can create perfusion defects, and you don't want to give the patient an incorrect diagnosis in this case. So in this case, we checked, we looked at the CT attenuation correction and made sure that the PET images were registered appropriately. The ejection fraction at rest, 70%, and at stress decreased to 67%, and you may appreciate that in the areas where there's a perfusion defect, there is a slight abnormality in wall motion, so mild hypokinesis in the hyperperfused segments. Myocardial blood flow analysis, normal resting myocardial blood flow, and then peak flow in the LAD, which is the area where we are concerned about, is significantly reduced. However, in the circumflex and RCA, the peak blood flow is normal. And looking at the reserve reduced in the LAD however normal globally. The way you you would look at this is this is likely a single vessel disease involving the left anterior descending artery. And this is again showing the myocardial flow reserve in the area where there is a perfusion defect shows a reduction in MFR to 1.4 again supporting the fact that this is a true defect and less likely to be artifactual. So the study interpretation was a large reversible perfusion defect in the LAD territory with mild hypokinesis in the hyper perfused segments during stress. However the patient did have a good prognostic marker in a sense that her global MFR was greater than 2 which effectively rules out multi-vessel disease. However the large ischemic defect and the lack of EF augmentation with stress is is considered an adverse prognostic marker. And this patient underwent catheterization and there is as you can appreciate a significant proximal LAD stenosis here and the patient underwent successful revascularization and her symptoms resolved. So going on to case 5 this is a 58 year old male with a history of type 2 diabetes hyperlipidemia hypertension and encephalopathy was referred for preoperative risk stratification prior to listing for kidney transplant. So just to give you a moment to look at the images resting images completely normal homogenous the stress images are also were interpreted as normal but the quality of the images were was not as good compared to the to the rest. So looking at the EKG response it was normal no abnormal STT changes the coronary calcium score was elevated at 745 and then the ejection fraction at rest and stress was essentially unchanged with normal wall motion. Looking at the myocardial blood flow the stress and rest flows were essentially the same the reserve was less than one. So the the two main differentials here are either a patient with significant multi-vessel disease or a patient who is an unresponder whether physiologically or due to caffeine intake or other medications that counteracted the effects of Raggedenison. So in this case the patient was questioned about their the their caffeine intake and indeed they they did admit to or he admitted to drinking a small caffeinated drink the night prior to the test. So the way we interpreted this study was we said this is even though this is a normal perfusion study however the lack of EF augmentation and the severely reduced MFR was suspicious for non-responder to Raggedenison and we recommended the test to be repeated. So we advised the patient to abstain from caffeine for 48 hours this is especially important for patients who drink caffeine on a regular basis just stopping caffeine for 12 or 24 hours may not be sufficient and so 48 hours of caffeine abstinence was recommended however similar results were obtained and the patient was deemed an unresponder in this case and eventually he underwent coronary angiography which showed non-obstructive atherosclerosis. The next case is a 70 year old male he has a history of coronary artery disease and prior angioplasty to the LAD was referred for chest pain evaluation. These are his images so looking at the rest and stress perfusion images the quality again compared to some of the other images we saw previously not the not the best there's it looks like there's a lot of blurring or haziness in the images and there is you guys can appreciate a I would say large moderate intensity fixed defect in the basal anterior anteroseptal anterolateral and also extending to the mid anterior and anterolateral and apical anterior segments no reversibility so it's a fixed defect the ejection fraction during rest was 65% increased to 73% with stress and there is no wall motion abnormality in the area where there is a perfusion defect so that so it's a bit of a head-scratcher. Now going to the myocardial blood flow analysis curves is important from a quality check to look at those to ensure there is a smooth curve no motion and and if you look at the flow curves and the inflow of the rubidium you can appreciate that in the top panel there is significant motion there is significant motion of the inflow so the patient probably moved significantly during this the scan probably respiratory although that can only be confirmed with the text but the the quality is not sufficient to to to provide an accurate diagnosis and you can see that the flow curves here are abnormal and not smooth and contour as I will demonstrate in the next couple of slides so the way the study was interpreted was there's a fixed defect in the anterior wall although with normal wall motion and there is significant motion seen on the myocardial blood flow cine images and so that the study was non-diagnostic and we recommended to repeat the study and as you can see here follow-up study was completely normal and the way we you know instruct these patients is if if if the patients are struggling with the side effects of Raggedenison we ask them to to try and control their breathing and not breathe deeply try to breathe as shallow as they as they can to minimize the respiratory motion and the the translation of the of the heart and just asking the text to go over this with the patient should help them sometimes you may need to give them anxiolytics as well but I think the key is to make sure there's good communication and setting the expectation with the patients just so they anticipate and they're aware of what is about to come or happen and then this is the blood flow the flow curves here are much smoother compared to the to the images we saw previously and the inflow of the rubidium on the top panel also it's very slight motion but nothing compared to what we saw before so we can be confident with with our interpretation of the of the images this time moving on to case seven this is a 52 year old female with COVID infection two months prior to presentation who is here for evaluation of chest pain so looking at the images rest and stress pet perfusion images you guys can notice I hope a significant defects a large defect severe intensity extending all the way from the base basal mid that so excuse me basal inferior inferior lateral infrared septal involving the mid as well and apical lateral segments very extensive involvement very extensive abnormalities also probably transient ischemic dilation seen here as well and ejection fraction with rest and stress 53% and 58% with stress however the areas where there is a perfusion abnormality so in the base on mid inferior and for lateral walls there is a hypokinesis with with stress the EKG response with abnormal with one millimeter horizontal ST depressions in the inferior leads and the coronary artery calcium score was was zero again make sure whenever you see this is you you you're comfortable with the quality check of the images and the overlay of the CT scan with the pet perfusion images to ensure there's no miss misregistration basically my cardio blood flow analysis so resting my cardio blood flow normal the peak flow is abnormal in all the territories but predominantly in the circumflex and RCA which is the area we were concerned about in terms of the perfusion defect the my heart of blood flow reserve in the LAD was normal however the global my cardio flow reserve is is reduced at 1.4 so putting it all together with whether this is multi-vessel involvement there's arguments for and against four is the MFR obviously less than 1.5 the extensive perfusion defect however calcium score of zero young age of the female augmentation of the LVF with with stress would argue against it so this could be end of significant endothelial dysfunction and significant obstructive stenosis in the circumflex and or RCA territory so the study interpretation was a large 20% ischemic defect in the circumflex territory with wall motion abnormalities in the hyperperfused segments and the prognostic markers so the abnormal MFR is an adverse prognostic marker however the good EF augmentation and the lack of calcium is a good prognostic marker for the patient and on coronary angiography as you can appreciate there is a significant severe stenosis in the OM branch it's a large OM branch actually and which was successfully revascularized with resolution of the symptoms the RCA was unremarkable on coronary angiography so the defect was predominantly in the circumflex territory so this is the summary of the teaching points that we discussed in the cases previously some of the high risk markers on pet myocardial perfusion imaging are the large perfusion defect size transient ischemic dilation reduction in injection fraction with stress or even lack of augmentation and the reduced global myocardial flow reserve less than two in general and definitely significantly high risk is as less than 1.5 which could point to my multi-vessel disease pet myocardial blood flow can aid in the discrimination between single vessel and multi-vessel disease as we saw in one of the cases where there was a reduction in the myocardial flow reserve in one territory with preservation of the blood flow in the two remaining territories and a normal global MFR which is supportive of a diagnosis of single vessel disease and motion is or can result in perfusion defects and it can make the myocardial blood flow assessment inaccurate so if you suspect that the quality of the images and the myocardial blood flow is abnormal do not report these numbers because you may mislead the referring providers but make sure you either interpret the perfusion images and just say that the myocardial blood flow cannot be interpreted due to quality abnormalities or you just report the study as uninterpretable if there is significant motion artifact that for instance interferes with interpretation of both the perfusion images and the myocardial blood flow analysis so that's all from from me thank you very much for listening I hope you found these cases very helpful

Dr. Talal El-Nabulsi

University of Kentucky

rubidium myocardial perfusion PET imaging

prognostic markers

coronary artery disease

myocardial flow reserve

motion artifacts