Non Invasive Quantification of Manganese Deposits in the Rat Brain by Local Measurement of NMR Proton T1 Relaxation Times

Abstract

Up to now, there is no reliable non invasive biomarker for the concentration 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 quantitative estimation of the concentration of Mn in brain. The relationship of the proton relaxation rates (1/ T 1) was established in rat brain homogenates as a function of the Mn, iron, and copper concentration. Subsequently, an experimental model of Mn neurotoxicity was used: rats were stereotactically injected with increasing amounts of Mn 2+ (as MnCl 2) in the ventricles. After 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 cerebellum 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 relaxation rates and tissue Mn concentrations (r = 0.84, 0.77 and 0.92 for the striatum, the cortex and the cerebellum, respectively). This methodology offers a unique tool for monitoring the degree of Mn concentration in different areas of the brain in animal models of Mn intoxication. It will be useful for evaluating the efficacy of treatments aimed at decreasing the metal in the brain. The method could be potentially useful for being transposed in the clinical situation for monitoring Mn-exposed workers.