Manganese is a useful contrast agent for MRI of animals. Previously, it has been shown that systemic doses of MnCl(2) provide unique contrast in the rodent brain, enabling visualization of neuroarchitecture. The present work investigates the dose and temporal dependence of brain enhancement after i.v. administration of MnCl(2). Varying doses of MnCl(2) (9-175 mg/kg) were administered to mice from 0 to 24 h prior to T(1)-weighted manganese-enhanced MRI (MEMRI) at 11.7 T. Pre-MnCl(2) T(1) values measured in different brain regions ranged from 1.17 +/- 0.03 to 1.76 +/- 0.01 s. Post-MnCl(2) T(1) measured 24 hr after administration of MnCl(2) were significantly decreased, even after the lowest dose of MnCl(2). The largest decreases occurred in the pituitary gland, where post-MnCl(2) T(1) ranged from 231 +/- 23 ms following the lowest dose to 143 +/- 43 ms after the highest dose, while the smallest decreases were observed in cortex (post-MnCl(2) T(1) = 1060 +/- 5 ms for low dose and 637 +/- 5 ms for high dose). The contrast resulting after 14 hr did not change up to 24 hr. Enhancement first occurred in subarachnoid spaces, followed by ventricles and periventricular tissues, and finally reached the remainder of the brain. Cortical layers were detected at higher doses (>88 mg/kg) and olfactory bulb layers were detected with the lowest dose (9 mg/kg). Temporal evolution of the enhancement of the olfactory bulb layers was observed. In some regions of the brain, such as hippocampus and thalamus, the changes in contrast detected between 2 and 14 hr used very specific pathways. These results demonstrate that both the dose and the time after MnCl(2) can be manipulated to optimize brain contrast in a region-specific manner.
(c) 2005 Wiley-Liss, Inc.