Reduced intracellular mobility underlies manganese relaxivity in mouse brain in vivo: MRI at 2.35 and 9.4 T

Using T1-weighted MRI at two different magnetic field strengths, the enhanced longitudinal relaxivity due to paramagnetic manganese ions in mouse brain in vivo is shown to reflect reduced intracellular mobility. One day after systemic administration of manganese chloride, increases of the longitudinal relaxation rate ∆R1 in several brain regions are significantly higher at 2.35 T than at 9.4 T. The corresponding relaxivity ratios 100r1/400r1 = 100∆R1/400∆R1 range from 2.4 (striatum) to 4.4 (cerebellar cortex). In contrast, the ∆R1 values after intraventricular administration of gadolinium-DTPA (Gd-DTPA) are not significantly different between both field strengths yielding 100r1/400r1 ratios from 1.0 to 1.1. The same observation holds true for manganese and Gd-DTPA relaxivities in aqueous solution. The pronounced field strength dependence of manganese relaxivities indicates a reduced mobility of manganese ions in vivo by confinement to a viscous fluid compartment and/or due to macromolecular binding. Moreover, preferential enhancement of nerve cell assemblies by manganese ions and the observation of additional contrast enhancement by magnetization transfer suggest an intracellular localization of manganese. This is further supported by a slow release of manganese from nerve cells postmortem, which occurs despite a high permeability of damaged cellular membranes as demonstrated by a rapid uptake of extracellular Gd-DTPA.