MRI assessment of brain iron content as a biomarker of methamphetamine toxicity

Oregon Health & Science University, Portland OR

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Abstract

DESCRIPTION (provided by applicant): Methamphetamine (MA) abuse produces long term changes to the dopamine system that likely contribute to the psychiatric symptoms and cognitive deficits that are seen in MA users. Recent studies in animal and in vitro models have provided preliminary evidence that brain iron accumulation may play a role in MA toxicity, both as a biomarker of damage and a potential source of increased oxidative stress. However, this relationship between MA toxicity and brain iron accumulation has not yet been characterized in human MA users nor has there been any investigations of the functional significance of this increase in iron accumulation. The goal of this research is to utilize in vivo magnetic resonance imaging (MRI) 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. The presence of iron shortens the transverse relaxation time constant (T2) of nearby water protons causing a loss of signal intensity on T2-weighted images. Preliminary findings from our group have demonstrated that former MA users have decreased T2-weighted signal intensities in the striatum compared to aged-matched, healthy controls. These signal intensity measurements inversely correlated with the reported dosage of MA used. These results support the thesis that brain iron content is increased in human MA users. However, while T2 weighted signal intensities are strongly influenced by tissue iron content, other factors play a role. Therefore, a prospective study is necessary to replicate these preliminary findings using MRI techniques that are more sensitive and quantitative for iron and to investigate the associations of these measures with neuropsychological deficits and psychiatric symptoms.