Fractionated manganese-enhanced MRI

Abstract

We investigated the use of manganese-enhanced MRI (MEMRI) with fractionated doses as a way to retain the unique properties of manganese as a neuronal contrast agent while lessening its toxic effects in animals. First, we followed the signal enhancement on T1-weighted images of the brains of rats receiving 30 mg/kg fractions of MnCl2 . 4H2O every 48 h and found that the signal increased in regions with consecutive fractionated doses and ultimately saturated. Second, we used T1 mapping to test whether the amount of MRI-visible manganese that accumulated depended on the concentration of manganese in the fractions. For a fixed cumulative dose of 180 mg/kg MnCl2 . 4H2O, increasing fraction doses of 6 x 30 mg/kg, 3 x 60 mg/kg, 2 x 90 mg/kg and 1 x 180 mg/kg produced progressively shorter T1 values. The adverse systemic health effects, including complications at the injection site and poor animal well-being, also rose with the fraction dose. Thus, fractionated MEMRI can be used to balance the properties of manganese as a contrast agent in animals against its toxic effects.

Figure 1

Region-of-interest (ROI) definitions for different brain structures. Representative coronal (Top) and horizontal (Bottom) slices from a 3D T₁-weighted image of a control rat and a rat following a 180 mg/kg injection of MnCl₂·4H₂0 showing regions analyzed in the study. Each region extends through multiple slices and corresponding ROIs were also defined in the coronal T₁ maps.

Figure 2

The effect of increasing numbers of fractions of MnCl₂ ·4H₂0 on the magnitude signal intensity in T₁-weighted images. (Top) Representative coronal and horizontal slices from 3D T₁-weighted images of a rat at each cumulative dose. (Bottom) A graph showing the magnitude signal from each brain region normalized to its value in the muscle surrounding the skull (error bars are standard deviations, n=4). The asterix denotes the manganese-injected groups of rats were significantly different from the control group (p≤0.05) – there were no significant differences between the injected groups.

Figure 3

The effect of increasing the dose of fractions of MnCl₂ ·4H₂0 on T₁ and magnitude signal intensity in T₁-weighted images. (Top) Representative coronal and horizontal slices from 3D T₁-weighted images of rat at each dose fraction. (Bottom) The T₁ in regions of the brain for control rats and rats from each dose fraction group at a total cumulative dose of 180 mg/kg MnCl₂·4H₂O (error bars are standard deviations, n = 4). The asterix denotes the manganese-injected groups of rats were significantly different from the control group (p≤0.05) – there were no significant differences between the injected groups.