 a very good morning to everyone. I'm so glad all of you could join today for this session but I'm going to review, I'm going to provide a short review of literature and critique the late cadillain enhancement quantification techniques on cardiac MR. Focus a little bit on quantification or fibrosis quantification in patients with myocarditis and their outcomes and also present a discussion of our study that I presented at the SCMR 2021 meeting last year on the COVID vaccine related myocarditis study. To begin, late cadillain enhancement cardiac MR imaging is an outstanding method to identify fibrosis in patients with ischemic and non-ischemic cardiomyopathies. The amount of fibrosis correlates with the risk of major adverse cardiovascular events. This is a publication in Jack that looked into the prognostic value of cardiac MR tissue characterization in risk stratifying patients with suspected myocarditis and they reported that the presence of LGE was associated with a more than a doubling risk for major adverse cardiovascular events. When accounting for other variables, LGE presence still maintained a significant association with MACE and the hazards ratios found to be 1.72. The major adverse cardiovascular events were pertaining to either all cause death or heart failure, decompensated heart failure requiring hospitalizations or patients needing heart transplantations or patients who had a documented sustained ventricular arrhythmia or patients who developed recurrent acute myocarditis based on elevated labs or absence of coronary artery disease and the presence of myocarditis based on the CMR criteria. To quantify LGE, several methods have been proposed such as the full width at half maximum thresholding based on 2, 3, 4, 5, 6, 8 standard deviation above the removed myocardium or a manual contouring of the enhanced myocardium which is the most variable where the thresholds will also vary per patient. Earlier an older publication in Jack again looked into the techniques for quantification of the myocardial scar in patients with ischemic and non-ischemic cardiomyopathy. The cohort consisted of hypertrophic cardiomyopathy in the non-ischemic cohort and acute and chronic myocardial infarctions in this chemico heart. The reported that out of all the techniques the reproducibility was worse in non-ischemic cardiomyopathies and ischemic cardiomyopathies. Full width by half maximum technique was the most reproducible even in the HCM patients however the intra-class correlation with this technique was reported as moderate of 0.7. This is another landmark paper in the journal of cardiovascular magnetic resonance where it was reported that the amount of LGE outperforms the current guideline recommended criteria in identifying patients of HCM that are at a risk of sudden cardiac death. The method used in this paper was 6 standard deviation as compared to the previous paper where it was full width by half maximum that was proposed to be more accurate. Scar was quantified into subcategories and it is universally known that higher the scar about more than 15% as a cutoff. These patients would definitely need intervention and placement of defibrillators since they are at a risk of sudden cardiac death. The paper we would like to focus today is again published in the journal of cardiovascular magnetic resonance where the comparison is performed for myocardial fibrosis quantification methods on cardiac MR to risk stratify patients with suspected myocarditis by granitone. This was a retrospective analysis of 670 patients with suspected myocarditis. All the various methods for quantification were applied on the images available. Late gadolinium enhancement for the visual presence score was also assessed and the strength of association of all these LGE results with major adverse cardiovascular events was determined. Inclusion criteria for these patients where when they had a suspected myocarditis and with signs and symptoms as either acute chest pain syndrome with a symptom onset less than two weeks before the cardiac MR or a sub-acute onset of symptoms of dyspnea or LV dysfunction or ventricular arrhythmias or an abnormal ECG. Exclusion criteria was a presence of a coronary artery disease or other non-ischemic cardiomyopathies such as HCM, ARVC, sacroid, amyloidosis, tachyzobocardiomyopathy, constructive pericarditis and so on and so forth. Now this is an interesting image we should focus on. The image A shows a faint sub-epicardial scar in the anterior antroceptum in the antrolateral segment and the inferior and the infroceptal segment. For the standard deviation techniques, the ROI is placed in a remote myocardium that is a non-enhanced normal myocardium. This was a lateral wall in this patient. For the full width half maximum, the ROI is placed in the enhanced fibrosis region. If you look carefully into the analysis, the amount of fibrosis is highest in two standard deviation that is significantly higher as compared to three standard deviation or the full width half maximum technique and these three methods have a higher scar as compared to four standard deviation. The amount of fibrosis declines for the around five, six and seven standard deviation. So on a single image there's so much of variability in quantification. When analyzing across the patients, it was mentioned that the greatest amount of LGE was measured with two standard deviation and leased with seven standard deviation technique. When you look into the values, the full width by half maximum technique, which is usually the most reproducible method, seems to be closer to the quantification to three standard deviation. Two standard deviation definitely has a higher amount of scar on an average. When we looked into the image quality parameters in these patients, it was reported that about 80% of these patients had good to excellent quality of their images. So on the results, 98 patients experienced major adverse cardiac events on a follow-up of about five years and association with the base was found with full width half maximum, two standard deviation and three standard deviation techniques with a hazards ratio of 1.05. Presence of the LGE also had an association with MACE and the hazards ratios 1.09. Four, five, six, seven standard deviation methods did not read significant association. But based on my previous discussion, the amount of scar was highest in two, three standard deviation and the full width half maximum technique in these patients. So it wouldn't be very surprising that a higher amount of scar was associated with more amount of adverse events in these group of patients and these values had a significant association. When a multivariable model was used and adjusted for 8 sex BMI and LB ejection fraction, full width half maximum technique, two standard deviation and the presence of LGE were associated with MACE and the three standard deviation technique was not reported. Highest degree of intrarator reproducibility and intraclass correlation was found for full width half maximum method that's already known in the literature. Coming to the discussion in this paper, it was mentioned that different LGE extent quantification methods result in different extent of myocardial fibrosis and that these methods are not interchangeable. The thresholds that use lower standard deviation cutoff may overestimate the extent of LGE. So it's not accurate. As we saw in the paper, there was no manual analysis of the scar. So there was no understanding of what was the accurate amount of scar because we know in patients with myocarditis, there'll be presence of edema as well. There'll be presence of T2 shine through and all those things that can lead to all these semi automatic quantification methods to give different to throw different amounts of scar to radiologists who is reading these images. It was also mentioned that if it's a patient of myocardial infarctions, LGE when is bright, apart from full width half maximum techniques, higher standard deviations are going to be accurate to estimate the amount of scar rather than fight to standard deviation. However, in patients with myocarditis, lower standard deviation methods may be able to capture edema fibrosis and diffuse fain scar that may not be visible in general to the naked eye. Again, it's was mentioned that the manual contouring of the late cadolinium enhancement extent may be less consistent than the semi automatic quantitative methods in sizing the LGE of patients with myocarditis. And at the end, image quality parameters have to be considered with selecting methods for LGE quantification. So to understand what are these image quality parameters that you need to know while you're trying to establish the amount of LGE on cardiac MR. So these include the signal to noise ratio contrast to noise ratio and the signal enhancement percentage. The formulas are pretty simple. You need a source image, a magnitude image. You place your ROI in the air to understand the noise. You place ROI on the remote myocardium and you place a region of interest on the enhanced myocardium to understand what are the image quality parameters and then analyze your image quality. Now, these are my cases where we have tried to identify, analyze fibrosis in different sets of patients, ischemic and non-ischemic. There's a patient with hypertrophic cardiomyopathy. We analyze the image quality to be having a low contrast to noise ratio and low signal enhancement percent. In this patient, five standard deviation was more closer to manual quantification of the scar, full with tough maximum underestimated the scar. This is an example of an ischemic cardiomyopathy patient. One set on the right on the left is having a higher better image quality, higher signal enhancement percent and higher contrast to noise ratio. Images here on the right, they have a lower signal enhancement percentage and the lower contrast to noise ratio. On the semi-quantitative analysis, it was found that if you have a higher or a better image quality, full width by half maximum technique is going to be more accurate and closer to the manual analysis of the scar. If the images are not so high in quantity, the five standard deviation method, as in this example, was able to perform very well and have a better correlation with the manual contouring of the scar and not so much for full width half maximum technique, which underestimated the scar. So to summarize, the five to six standard deviation methods will perform well when the images have low signal enhancement percent or contrast to noise ratio. This analysis may be able to, we will be able to replicate in patients with myocarditis and also able to understand their outcomes related to means. Full width half maximum technique can be used when as it relies on the scar being bright and then can be used to delineate scar accurately in such patients. It can underestimate the scar if you do not consider image quality parameters. It may be inaccurate in case of faint scar. The limitations for all the studies that we have seen in the literature is that a gold standard is lacking. There is no histopathological confirmation to the amount of fibrosis and what the cardiac MR quantification techniques are being able to show us. So our take home message from this exercise is that we need to be cautious when quantifying myocardial scar in any group of patient, whether it's chemic or non-schemic, and the assessment should always be guided on the basis of image quality parameters. Now, based on this discussion, we move forward and look into the study that we presented at the Society of Cardiovascular Magnetic Resonance this year in 2021, where we compared the clinical and the cardiac MR biomarkers in children presenting with acute chest pain and elevated troponins diagnosed as atypical myocarditis in the pre-COVID era, comparing them to post-COVID vaccine-associated myocarditis. It's been known that myocarditis or atypical myocarditis, which is presenting as acute chest pain with elevated troponins in children who were previously asymptomatic, is quite rare. However, recently in the last two years, it has been reported in association, I'm sorry, with the COVID-19 vaccine with a Pfizer or Moderna. The Center for Disease Control and Prevention, this is reviewed on November 9, 2021. It was mentioned that there has been an increased cases of myocarditis and pericarditis in the United States after the mRNA vaccination with Pfizer or Moderna. This was more prevalent in adolescents and young males. This paper in the New England Journal of Medicine reported the incidence of such myocarditis as 2.13 cases per 100,000 people. Highest incidence was amongst male between the age of 16 to 29 years. We aim to compare our clinical biomarkers and cardiac MR imaging features in children with isolated chest pain with elevated troponin, representing atypical myocarditis in the pre-COVID era with those who developed vaccine-associated myocarditis after receiving the COVID vaccine. Now, this was a single center retrospective study. Clinical and baseline, 1.5 Tesla cardiac MR data was acquired within 30 days of symptoms and five months of follow-up was also available. CMR analysis was performed using circle CVI software. In both the groups, the age of the patient did not differ significantly and it was on an average of 15 years. Most of the patients were males. The body surface area was found to be higher in patients with COVID vaccine-associated myocarditis and ECG anomalies and the troponin values did not differ significantly in these patients. The highest troponin values in the atypical myocarditis in the pre-COVID era patients was about 12 nanograms per ml. It was about 9.2 nanograms per ml in the vaccine-associated myocarditis patients. Brain atrialitic peptide representing dilated cardiomyopathy or decompensated heart failure was higher in patients in the pre-COVID era with atypical myocarditis. This difference was statistically significant in between the groups. The image quality of our cohort, majority of the patients had either a low to moderate contrast to noise ratio and signal enhancement percent. On the base of our image quality and on base of a small pilot study, we analyzed the late gadolinium enhancement in these patients using the five standard deviation technique. Coming to our results, the cardiac MR that was available in 21 patients in the atypical pre-COVID myocarditis group was obtained from 2012 to 2019. That was a longer duration. In patients that had a COVID vaccine-associated myocarditis, the data was acquired in like three months. End-astolic volumes were higher in the pre-COVID era patients with myocarditis and the ejection fraction did not differ significantly or the LV ejection fraction did not differ significantly in these patients. Edema was present in all of them. Most of the patient had a normal ejection fraction in both the groups. The characteristic site for late gadolinium enhancement was sub-epicardial in both the groups. Some of the patients also had mid-myocardial to sub-epicardial enhancement. Some of the patients had a characteristic pericardial enhancement. The percent of late gadolinium enhancement or the amount of fibrosis quantified on CMR was higher in patients with a pre-COVID atypical myocarditis group of about 25% and on an average 10% in patients that had a vaccine related myocarditis. Native T1 mapping values were elevated in both the groups and it was higher in the pre-COVID atypical myocarditis group although the difference was not statistically significant. The extracellular volumes were also higher in the pre-COVID atypical myocarditis group and the difference was statistically significant. T2 mapping was available only in the vaccine related myocarditis group and it was higher in these patients. Strain analysis on cardiac MRs also performed and all the strain parameters were abnormal when compared to normal strail assessments on the same scanner with the 150 patients cohort. The abnormal values did not differ significantly in between both the myocarditis groups. Now coming to the cases, so this is an example of a pre-COVID atypical myocarditis patient. This was a 17-year-old male presented to the emergency in the pre-COVID pandemic with acute chest pain, elevated troponins and non-specific ECQ findings. Image A and B is the first acquisition, C and D is the follow-up acquisition. Cardiac MR showed sub-epicardial enhancement in the lateral and the inferior walls that amounted to 22% of fibrosis. The LV ejection fraction was normal. Native T1 values were significantly elevated and the extracellular volume was not so much, only mildly elevated in this patient. Patient was treated with IV neuroglobulins and steroids and there was a significant resolution of the LGE six months later as you see. This is another case but this is a patient who developed post-COVID vaccine associated myocarditis, again a 17-year-old male patient. He presented two days after receiving the COVID vaccine with acute chest pain, elevated troponins and ECG ST elevations. On cardiac MR, the amount of LGE was found to be 7.8%. The pattern of LGE was against sub-epicardial location in the inferior and the lateral walls from base to apex. Strain analysis was also performed. It was abnormal in this patient. Native T1 values was elevated. This was the first acquisition. This is the follow-up acquisition image D, E and F. On the follow-up cardiac MR, this was after three months. There was a near complete resolution of the late gadolinium enhancement and the LV ejection fraction also improved mildly from 51 to 54%. This is another case with a more severe or more significant amount of enhancement after receiving COVID vaccine. This was a 16-year-old male patient. Again presented with chest pain, elevated troponins, ST elevation lateral leads. He received a Pfizer COVID vaccine and he presented three days after receiving the vaccine. On cardiac MR, this sub-epicardial LGE quantification, the LGE was present in the sub-epicardial to mid-myocardial location in the inferior and the infralateral wall. The quantification analysis was 26% for presence of fibrosis. LV ejection fraction was okay. Native T1 values were mildly elevated. ECB was not so much elevated. T2 values were significantly elevated to 64 milliseconds. A follow-up cardiac MR, the lower images are of the follow-up cardiac MR and the LGE did show a decline, which can also be found just on visual assessment. This was four months later. The LV ejection fraction was stable. This is an example of how a strain measurement is performed. You usually perform it on the two-chamber view, four-chamber view, and the short axis view. This two-chamber view is showing you a longitudinal strain. In this patient, the strain analysis was abnormal on the first acquisition and it improved mildly on follow-up. We also analyzed the follow-up data and we found that the LGE was present after a follow-up of about 18 months in the first group and about three months in the second group. LGE was present in about 60% to 70% of the patients. But whenever it was present, it did show a decline in all of them. A quantitative analysis was also available later on, but I have not included in the slides, but I know it did show a decrease in all of them. Ejection fraction was okay in most of the patients on initial examination on follow-up. The coming to the limitation of the study, the cardiac MRs that were acquired in the pre-COVID era were most likely to be limited to patients who had a severe disease with higher late-cadolinium enhancement who were not responding to NSAIDs. Again, we have a small size of the patients and there's a limited follow-up and we need longer follow-up to conclude more on the basis of this study and other previous studies that are present in the literature. We conclude that in patients with post-COVID vaccine-related myocarditis, a low threshold exists for performing cardiac MR because they are less edema, less late-cadolinium enhancement, and less effect on the cardiac size and function. And we concluded that no significant differences in demographics, troponine, and the cardiac MR parameters were present in this pre-COVID atypical myocarditis when compared to the post-COVID vaccine-related myocarditis in the adolescent males. The future prospects include we need a long-term multi-center study to see if there are these smaller elevations in T-22 and the lab markers. The return of the LV ejection fraction and disappearance of LGE in follow-up cases occurred that could suggest a more benign course in children post-COVID vaccine as compared to those who had an atypical myocarditis in the pre-COVID era. We certainly need follow-up cardiac MR for predicting long-term outcomes in any of these groups. Thank you for your attention. I am open to questions. Thank you Dr. Avanti for taking us to an interesting article that was excellent really. No questions currently but I'm sure people can reach out to you if they have any queries. Absolutely. So we have the entire session available for y'all on the Indian Radiologist YouTube channel as well so y'all can go back and review the article again. Also the link for today's article has been shared in the chat box so you can go ahead and please access that. And the detailed question for the Oncoimaging update in April as well as other masterclass events has also been provided in the chat box. If you do have any questions regarding today's article you can reach out to me Dr. Mithusha or Dr. Avanti. There are a couple of positive and praises coming in for you in the chat box. Excellent presentation. So thank you Avanti for making time for us and being here with me today. And yeah feel free to reach out to me, email me on my UW account or my Gmail account. I'm always there if you had any queries and if you need to understand more on the quantification. Dr. Avanti I think if you could leave your email in the chat box. Okay the details for registration for the events is available on the ideologist channel website as well. Before we move on I would once again like to thank our entire team at Indian Radiologist Dr. Patkarsar, Dr. Manisa, Dr. Shalendra Singh and Dr. Jignesh Thakur for giving us this platform. My colleagues Dr. Mithusha Verma, Mamta Ma'am, Dr. Amit Poonkar for always being there. Avanti for joining us today and joining our team of the Radiology Masterclass for the Radiology Journal Club events. Thank you all once again and big thank you to our educational partners, Bayers and Phantom Healthcare. Thank you everyone and we'll see you all next month with another Journal Club. Dr. Amit I think we can have the sponsor videos once more. Thank you. 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