Manganese-Enhanced Magnetic Resonance Imaging of the Heart

Abstract

Manganese-based contrast media were the first in vivo paramagnetic agents to be used in magnetic resonance imaging (MRI). The uniqueness of manganese lies in its biological function as a calcium channel analog, thus behaving as an intracellular contrast agent. Manganese ions are taken up by voltage-gated calcium channels in viable tissues, such as the liver, pancreas, kidneys, and heart, in response to active calcium-dependent cellular processes. Manganese-enhanced magnetic resonance imaging (MEMRI) has therefore been used as a surrogate marker for cellular calcium handling and interest in its potential clinical applications has recently re-emerged, especially in relation to assessing cellular viability and myocardial function. Calcium homeostasis is central to myocardial contraction and dysfunction of myocardial calcium handling is present in various cardiac pathologies. Recent studies have demonstrated that MEMRI can detect the presence of abnormal myocardial calcium handling in patients with myocardial infarction, providing clear demarcation between the infarcted and viable myocardium. Furthermore, it can provide more subtle assessments of abnormal myocardial calcium handling in patients with cardiomyopathies and being excluded from areas of nonviable cardiomyocytes and severe fibrosis. As such, MEMRI offers exciting potential to improve cardiac diagnoses and provide a noninvasive measure of myocardial function and contractility. This could be an invaluable tool for the assessment of both ischemic and nonischemic cardiomyopathies as well as providing a measure of functional myocardial recovery, an accurate prediction of disease progression and a method of monitoring treatment response. EVIDENCE LEVEL: 5: TECHNICAL EFFICACY: STAGE 5.

Keywords: calcium handling; kinetic modeling; manganese-enhanced magnetic resonance imaging.

FIGURE 1

Manganese uptake in the body. Manganese‐enhanced images (a) at native T1 and post‐manganese T1 (30 minutes) demonstrating manganese enhancement in the liver (L), pancreas (P) and kidneys (K). Conversely, little enhancement is seen in skeletal muscle (SM). T1 decay curves (b) demonstrate greatest reduction in T1 in liver (green), followed by pancreas (light blue), kidney (green), heart (red) and skeletal muscle (dark blue). Dotted line represents end of manganese dipyridoxyl diphosphate infusion. Manganese uptake (c) in liver (green), pancreas (light blue), kidney (green), heart (red) and skeletal muscle (dark blue).

FIGURE 2

Types of manganese‐based contrast media. Manganese chloride (a), manganese gluconate (b), manganese dipyridoxyl diphosphate (c) and O‐carboxymethyl chitosan manganese‐diethylenetriamine pentaacetate are examples of nonchelated and chelated manganese‐based contrast agents, respectively. MnCl₂ = manganese chloride; EVP 1001‐1 = manganese gluconate; MnDPDP = manganese dipyridoxyl diphosphate; CMCS (Mn‐DTPA) = O‐carboxymethyl chitosan manganese‐diethylenetriamine pentaacetate.

FIGURE 3

Myocardial calcium homeostasis and manganese uptake. Calcium homeostasis in normal myocardium (a) and manganese uptake via voltage‐gated calcium channels (b). Ca²⁺ = calcium ion; Na⁺ = sodium ion; H⁺ = hydrogen ion; Mn²⁺ = manganese ion; NCX = sodium–calcium exchangers; NHE‐1 = sodium hydrogen exchanger; RyR = ryanodine receptors; PLB = phospholamban; SERCA = sarcoplasmic reticulum calcium adenosine triphosphatase.

FIGURE 4

Manganese‐enhanced magnetic resonance imaging of healthy myocardium. Short‐axis T1 mapping in healthy myocardium with manganese dipyridoxyl diphosphate (a). Rapid reduction in T1 is seen in the blood pool (green, b), followed by rapid normalization by 30 minutes. In contrast, the T1 value of myocardium (red) shows steady and sustained reduction throughout the imaging time period (b). Dotted line represents end of manganese dipyridoxyl diphosphate infusion.

FIGURE 5

Patlak modeling. Patlak formulation—schematic of (a) model compartments and transfer constant K _i , describing passage from reversible to irreversible compartment (b) data analysis. C_m(t) = myocardial manganese concentration; C_b(t) = blood manganese concentration.

FIGURE 6

Manganese‐enhanced magnetic resonance imaging in acute myocardial Infarction. Short‐axis views of gadolinium‐enhanced, native and 30‐minute postmanganese T1 map images in patients with acute anteroseptal (a), anterior (b), and inferior (c) myocardial infarction. Gadolinium‐enhanced images demonstrate the presence of late gadolinium in the anteroseptal, anterior and inferior walls respectively. Conversely, manganese‐enhanced images demonstrate reduced manganese uptake (abnormal calcium handling, green) in the anteroseptal, anterior and inferior walls. Mean T1 decay times in bloodpool (green), infarct (red), peri‐infarct (orange) and remote region (blue) in patients with acute myocardial infarction (d). Mean myocardial manganese uptake (Ki‐ mL/min/100 g of tissue) defined by Patlak modeling in patients with acute myocardial infarction and healthy volunteers (e).

FIGURE 7

Calcium dysfunction in the failing myocardium. Several factors cause reduced calcium ion (Ca²⁺) release from the sarcoplasmic reticulum resulting in systolic heart failure (a). Diastolic heart failure results from reduced rate of Ca²⁺ removal causing delay in myocardial relaxation (b). Ca²⁺ = calcium ion; Na⁺ = sodium ion; H⁺ = hydrogen ion; Mn²⁺ = manganese ion; NCX = sodium–calcium exchangers; NHE‐1 = sodium hydrogen exchanger; RyR = ryanodine receptors; PLB = phospholamban; SERCA = sarcoplasmic reticulum calcium adenosine triphosphatase.

FIGURE 8

Manganese‐enhanced magnetic resonance imaging in ischemic and nonischemic Cardiomyopathy. Short‐axis views of gadolinium‐enhanced images (a), native T1 (b) and 30‐minute post‐manganese T1 maps (c) in patients with dilated and hypertrophic cardiomyopathy.

FIGURE 9

Cardiac magnetic resonance features of patients hospitalized with coronavirus disease‐19. Magnetic resonance imaging findings in patients recovering from COVID‐19 infection compared to age‐, sex‐, and co‐morbidity‐matched volunteers. MEMRI = manganese‐enhanced magnetic resonance imaging; LV = left ventricle; RV = right ventricle.