Time-course manganese chloride biodistribution and manganese-induced MRI contrast in mouse organs.

PURPOSE: To optimize manganese-enhanced MRI (MEMRI) in mice by profiling the time-course biodistribution and associated T1 contrast enhancement of MnCl2 injected subcutaneously to avoid abrupt spikes in blood manganese levels.

METHODS

Manganese (Mn) biodistribution and Mn-induced T1 contrast in healthy female adult CD-1 mice were investigated at two doses (0.2 and 0.4 mmol/kg) and 2, 6, and 24 h following injection. T1-weighted MRI and T1 mapping were performed at 3 T. The heart, liver, kidneys, leg skeletal muscle, lungs, spleen, and blood were collected and quantified for Mn content using inductively coupled plasma atomic emission spectroscopy. Toxicity was assessed on hematoxylin and eosin histological sections of the heart, liver, kidneys, lungs, and spleen.

RESULTS

An injection dose of 0.2 mmol/kg produced significant T1 enhancement in the heart, liver, and kidneys, reaching peak enhancement at 2 h following injection. Doubling the dose did not produce further T1 enhancement in the heart, liver, nor kidneys. Skeletal muscle reached peak enhancement at 24 h and required an injection dose of 0.4 mmol/kg. Inductively coupled plasma atomic emission spectroscopy-measured tissue-level Mn content corroborated MRI results and revealed peak Mn concentration also at 2 h following injection in the spleen, lungs, and blood. No organ toxicity was observed at either dose on histology.

CONCLUSION

The subcutaneous injection route provided substantial T1 contrast enhancement in all tissues investigated, without toxicity at the maximum dose of 0.4 mmol/kg tested. However, the injection dose and optimal postinjection imaging interval must be tailored to the organ of interest.