A model for the analysis of competitive relaxation effects of manganese and iron in vivo.

Manganese (Mn) and iron (Fe) are both paramagnetic species that can affect magnetic resonance relaxation rates. They also share common transport systems in vivo and thus in experimental models of metal exposure their effects on relaxation rates may interact in a complex fashion. Here we present a novel model to interpret the combined effects of Mn and Fe on MRI relaxation rates. To achieve varying levels of both metals, adult rats were separated into four groups; a control group and three groups treated with weekly intravenous injections of 3 mg Mn/kg body for 14 weeks. The three treated groups were fed either a normal diet, Fe deficient or Fe enriched diet. All rats were scanned using MRI at the 14th week to measure regional water relaxation rates. Rat brains were removed at the end of the study (14th week) and dissected into regions for measurement of Mn and Fe by atomic absorption spectroscopy. For the normal diet groups, R(1) was strongly correlated with tissue Mn concentrations. However, the slopes of the linear regression fits varied significantly among different brain regions, and a simple linear model failed to explain the changes in relaxation rate when both Mn and Fe contents changed. We propose a competition model, which is based on the ability of Mn and Fe to compete in vivo for common binding sites. The combined effect of Mn and Fe on the relaxation rates is complicated and additional studies will be necessary to explain how MRI signals are affected when the levels of both metals are varied.