Cardiac manganese-enhanced magnetic resonance imaging: cardiac MEMRI

Abstract

BACKGROUND: Manganese-based contrast media can provide intracellular T1 enhancement in viable tissues that have active calcium-dependent processes. Pre-clinical and early studies in man have demonstrated that manganese-enhanced magnetic resonance imaging has potential as a surrogate marker of myocardial calcium handling. The aims of this thesis are to investigate the feasibility and utility of manganese-enhanced magnetic resonance imaging of the myocardium in different aetiologies of ventricular dysfunction.

METHODS AND RESULTS: First, I assessed the repeatability of manganese-enhanced magnetic resonance imaging and its scan-rescan reproducibility. This has not been established and is a necessary step for its future clinical application. I assessed the intraobserver and interobserver repeatability of T1 mapping and kinetic modelling, and the overall scan-rescan reproducibility, of myocardial manganese-enhanced magnetic resonance imaging. I demonstrated excellent repeatability of manganese-enhanced T1 mapping and kinetic modelling in healthy and pathological myocardium. Furthermore, scan-rescan reproducibility of manganese-enhanced magnetic resonance imaging in healthy volunteers was excellent.

I next assessed manganese-enhanced magnetic resonance imaging in non-ischaemic cardiomyopathy in patient cohorts with either dilated or hypertrophic cardiomyopathy. Using kinetic modelling, myocardial manganese uptake demonstrated stepwise reductions across healthy myocardium, hypertrophic cardiomyopathy without fibrosis, dilated cardiomyopathy and hypertrophic cardiomyopathy with fibrosis. I demonstrated that manganese-enhanced magnetic resonance can distinguish between healthy and fibrosed myocardium, providing a non-invasive measure of myocardial calcium handling.

To date, there have been no studies assessing whether manganese-enhanced magnetic resonance imaging can detect alterations in myocardial calcium handling in acute takotsubo syndrome. I used manganese-enhanced magnetic resonance imaging to assess myocardial calcium handling in patients with takotsubo syndrome during both the acute presentation and following apparent recovery. I demonstrated that patients with takotsubo syndrome have a profound perturbation of myocardial calcium handling which is most marked in the acute setting but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial oedema.

Finally, the COVID-19 pandemic has had a substantial effect worldwide. Myocardial injury is common in patients hospitalised with COVID-19. However, the mechanisms underlying this are not well understood. Using both gadolinium-enhanced and manganese-enhanced magnetic resonance imaging combined with CT coronary angiography, I sought to determine the contribution and impact of pre-existing cardiovascular disease on the cardiac abnormalities of patients recovering from COVID-19 hospitalisation. Patients demonstrated right, but not left, ventricular dysfunction consistent with the dominant pulmonary pathology of this condition. Furthermore, no evidence of myocardial calcium handling was observed in patients. Previous reports of left ventricular myocardial abnormalities following COVID-19 are likely to reflect pre-existing co-morbidities rather than a direct consequence of COVID infection itself.

CONCLUSION: I have demonstrated excellent repeatability and reproducibility of manganese-enhanced T1 mapping and kinetic modelling in healthy and diseased myocardium. Furthermore, the scan-rescan reproducibility of manganese-enhanced magnetic resonance imaging in healthy volunteers was excellent, suggesting it has potential for clinical application. I described utility and feasibility of myocardial manganese-enhanced magnetic resonance imaging as a non-invasive measure of myocardial calcium handling in patients with non-ischaemic cardiomyopathy. In patients with takotsubo syndrome, I observed dysfunctional myocardial calcium handling which is most striking during the acute episode but persists despite apparent recovery of the heart. Finally, we have shown that patients with recent severe COVID-19 infection demonstrated right but not left ventricular dysfunction. This is likely secondary to long-term pulmonary sequelae of COVID-19. Furthermore, previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing co-morbidities.

Overall, I have demonstrated that manganese-enhanced magnetic resonance imaging holds major promise for the diagnosis, risk stratification and monitoring of cardiac disease, with the potential for the assessment of novel treatment interventions.