Manganese‐enhanced MRI of mouse heart during changes in inotropy†

Abstract

Recently the dual properties of manganese ion (Mn 2؉ ) as an MRI contrast agent and a calcium analogue to enter excitable cells has been used to mark specific cells in brain and as a potential intracellular cardiac contrast agent. Here the hypothesis that in vivo manganese-enhanced MRI (MEMRI) can detect changes in inotropy in the mouse heart has been tested.

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

“…In vitro studies in isolated cells (12,13) and in vivo mouse heart (14) demonstrate that Mn 2ϩ enters cells through ligand-or voltagegated Ca 2ϩ channels, an effect blocked by Ca 2ϩ channel antagonists. Once translocated, Mn 2ϩ remains intracellular for a prolonged period (15).…”

Magnetic resonance imaging, microscopy, and spectroscopy of the central nervous system in experimental animals

“…The increased versatility that microscopic resolution MRI is beginning to provide will lead to new insight into the processes that determine life and death and should result in the development of new diagnostic and treatment approaches in several human diseases. 31 P spectra of mouse spinal cord PCA extracts recorded using a 11.4 Tesla NMR spectrometer. Within 1 min (at least 1 min is necessary to freeze the spinal cord after animal sacrifice) most of the PCr is gone; also notable are increase of ADP, ␣-glycerophosphate (␣GP) and nucleotide monophosphates (NMP) (lines in phosphomonoester (PME) region).…”

“…The following metabolites are studied most frequently with MRS in CNS diseases: NAA for its role in mitochondrial oxidative metabolism, as a putative marker for neuronal viability and its role in lipid synthesis (source of acetyl groups); Cr (Creatine) and PCr (phosphocreatine) as creatine to phosphocreatine energy conversion is mediated by creatine kinase; choline (Cho) as a precursor for neurotransmitter acetylcholine and membrane phospholipids, phosphatidylcholine and sphingomyelin; myo-inositol (mI) as a neuronal signal- 31 P spectrum of rat brain in vivo, in deep hypothermia. Spectrum was recorded using a 9.4 Tesla (400 MHz for protons or 161.9 MHz for 31 P) NMR spectrometer with surface coil and was baseline corrected to eliminate background signal from the skull.…”

The role of imaging and molecular imaging in the early detection of metabolic and cardiovascular dysfunctions

“…Mn 2 þ uptake is increased by elevated heart rates because of adrenergic stimulation, whereas uptake is decreased in cases of increased Ca 2 þ concentration because of the presence of calcium blockers, such as verapamil and dihydropiridine (which is fairly specific for an L-type channel). 69,[72][73][74] The discovery that cardiotoxicity was mainly due to extracellular Mn 2 þ instead of intracellular Mn 2 þ and that the slow infusion of a low, non-toxic concentration of Mn 2 þ leads to high tissue accumulation prompts reuse of Mn-based contrast media for cardiac imaging. 75 Mn-enhanced cardiac MRI was then re-evaluated, particularly in the context of Mn 2 þ being a surrogate of Ca 2 þ uptake by cardiomyocytes.…”

“…Recent studies obtained promising results in differentiating viable from non-viable segments in showing different enhancement. 73,76 Hence, viable cells will take up Mn 2 þ , whereas dead cells will not (Figure 10). This differential uptake between the viable and non-viable cell could also be increased pharmacologically.…”