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.

Myocardial Viability Imaging using Manganese‐Enhanced MRI in the First Hours after Myocardial Infarction

“…Hence, a method to quantify calcium uptake within live cells, animals, and patients would provide valuable information on cardiac viability and insights into pathological and therapeutic mechanisms. [ 5,6,22 ]…”

Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells

“…Divalent manganese ions (Mn 2+ ) act similarly to other paramagnetic ions such as gadolinium or copper (Gd 3+ , Cu 2+ ), shortening the T1 relaxation and increasing signal intensity. Work on the use of Mn 2+ in MRI has been going on for decades and includes mainly imaging of the central nervous system [ 18 , 19 ], cardiovascular system [ 20 ], and cancer [ 21 , 22 ]. Routinely, manganese was used as a contrast in the form of manganese chloride, dissolved in water or NaCl [ 22 , 23 ] or as an FDA-approved contrast agent for human use—Mangafodipir [ 24 ] was usually administered intravenously, intraperitoneally, or intraparenchymally.…”

Functional Nanomaterials Based on Self‐Assembly of Endogenic NIR‐Absorbing Pigments for Diagnostic and Therapeutic Applications

“…The presence of Mn 2+ in the ZBMn NPs also provides the possibility of MRI. [ 44 ] Tumor‐bearing mice injected with the ZB NPs and ZBMn NPs were imaged by PAI and MRI, which show that the accumulation of the ZB NPs and ZBMn NPs in tumor sites reached the maximum at 6 h after the injections (Figure 3B,C). Quantitative analysis of the PAI signal revealed the better accumulation of the ZBMn NPs in tumors than that of the ZB NPs, which should be attributed to the better structural stability of the ZBMn NPs during circulation in blood.…”