Non invasive quantification of manganese deposits in the rat brain by local measurement of NMR proton T-1 relaxation times

Up to now, there is no reliable non invasive biomarker for the concentratio n of manganese (Mn) in the brain after intoxication to this metal. The aim of the present experimental study was to determine the predictive value of the localized measurement of the proton NMR relaxation time T-1 as a quanti tative estimation of the concentration of Mn in brain. The relationship of the proton relaxation rates (1/T-1) was established in rat brain homogenate s as a function of the Mn, iron, and copper concentration. Subsequently, an experimental model of Mn neurotoxicity was used: rats were stereotacticall y injected with increasing amounts of Mn2+ (as MnCl2) in the ventricles. Af ter 3 weeks, local measurements of T-1 were carried out in live rats. They were then sacrificed in order to sample the striatum, the cortex and the ce rebellum from the brain and to perform a quantitative determination of the concentration of Mn in these tissues by atomic absorption spectrometry (AAS ). The results indicate excellent correlation coefficients between relaxati on rates and tissue Mn concentrations (r = 0.84, 0.77 and 0.92 for the stri atum, the cortex and the cerebellum. respectively). This methodology offers a unique tool for monitoring the degree of Mn concentration in different a reas of the brain in animal models of Mn intoxication. In will be useful fo r evaluating the efficacy of treatments aimed at decreasing the metal in th e brain. The method could be potentially useful for being transposed in the clinical situation for monitoring Mn-exposed workers. (C) 2001 Elsevier Sc ience Inc. All rights reserved