Manganese-enhanced MRI of the myocardium

Abstract

Gadolinium-based contrast media are widely used in cardiovascular MRI to identify and to highlight the intravascular and extracellular space. After gadolinium, manganese has the second highest paramagnetic moment and was one of the first MRI contrast agents assessed in humans. Over the last 50 years, manganese-enhanced MRI (MEMRI) has emerged as a complementary approach enabling intracellular myocardial contrast imaging that can identify functional myocardium through its ability to act as a calcium analogue. Early progress was limited by its potential to cause myocardial depression. To overcome this problem, two clinical formulations of manganese were developed using either chelation (manganese dipyridoxyl diphosphate) or coadministration with a calcium compound (EVP1001-1, Eagle Vision Pharmaceuticals). Preclinical studies have demonstrated the efficacy of MEMRI in quantifying myocardial infarction and detecting myocardial viability as well as tracking altered contractility and calcium handling in cardiomyopathy. Recent clinical data suggest that MEMRI has exciting potential in the quantification of myocardial viability in ischaemic cardiomyopathy, the early detection of abnormalities in myocardial calcium handling, and ultimately, in the development of novel therapies for myocardial infarction or heart failure by actively quantifying viable myocardium. The stage is now set for wider clinical translational study of this novel and promising non-invasive imaging modality.

Keywords: MEMRI; manganese-enhanced MRI; viability.

Figure 1

Preclinical manganese-enhanced MRI (MEMRI). MEMRI T1 mapping of acute myocardial infarction in a preclinical model of myocardial infarction in rat, with MnDPDP. Colour maps are configured to show infarct (pink) and remote myocardium (green) with an intermediate peri-infarct zone (yellow). Note the visibly smaller infarct size with MEMRI compared with DEMRI, more in line with histological description of infarct with Masson’s trichrome (MTC). DEMRI, delayed-enhancement MRI; MnDPDP, manganese dipyridoxyl diphosphate.

Figure 2

Clinical manganese-enhanced MRI (MEMRI). MEMRI T1 mapping in healthy myocardium with manganese dipyridoxyl diphosphate. Rapid reduction in T1 is seen in the blood pool, followed by rapid normalisation by 40 min. In contrast, the T1 value of remote myocardium shows steady and sustained reduction throughout the imaging time period.

Figure 3

Clinical manganese-enhanced MRI (MEMRI) in a patient with myocardial infarction. Clinical tissue characterisation acutely post-myocardial infarction with native T1 mapping (A), MEMRI T1 mapping (B), gadolinium delayed-enhanced MRI (C) and manganese enhancement (D). Note shortened T1 in remote myocardium on MEMRI compared with native T1 mapping (A, B). Inversion recovery images demonstrate shortening in infarct with gadolinium (C) and in remote myocardium with manganese (D) (extent of enhancement indicated by arrows and dashed lines).