MRI assessment of brain iron content in methamphetamine users

Introduction: Methamphetamine (MA) abuse produces long term changes to the dopamine system that likely contribute to the psychiatric and cognitive symptoms that are seen in MA users. Emerging evidence from preclinical studies suggests that brain iron accumulation plays a role in MA toxicity, both as a biomarker of damage and a potential source of oxidative stress; however, this relationship has not yet been characterized in human MA users. The goal of this study was to utilize in vivo magnetic resonance imaging (MRI) techniques to measure brain iron levels in human subjects with a history of MA dependence and determine if these measurements represent functionally significant biomarkers of MA toxicity. Iron is paramagnetic, and its presence increases the transverse relaxation rate constant (R2) of nearby water protons causing a loss of signal intensity on T2-weighted images. Measuring this effect using quantitative MRI techniques allows for in vivo investigation of the effects of MA on the distribution of brain iron. Methods: MRI datasets were acquired from 27 currently abstinent MA users and 27 aged matched healthy control subjects. Series used in this study included a high-resolution, T1-weighted MPRAGE, T2-weighted TRSE, Turbo Spin Echo (TSE) sequences acquired with three different echo times and a 3D proton density (PD) sequence. R2 (≡1/T2) maps were calculated at each voxel using a monoexponential decay function. Maps of the fractional macromolecular (fM) content were created by normalizing PD images intensities to the peak intensity