Improved mapping of pharmacologically induced neuronal activation using the IRON technique with superparamagnetic...

The use of functional magnetic resonance imaging (fMRI) techniques for evaluation of pharmacologic stimuli has great potential for understanding neurotransmitter dynamics for a number of brain disorders, such as drug abuse, schizophrenia, epilepsy, or neurodegeneration. Unfortunately, blood oxygenation level-dependent (BOLD) imaging at common fields strengths, such as 1.5 or 3 T, has very low sensitivity and contrast-to-noise ratios (CNRs). We demonstrate here the utility of using an intravascular superparamagnetic iron oxide contrast agent with a long plasma half-life for evaluation of hemodynamic changes related to dopaminergic stimuli using amphetamine or the cocaine analog 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT). We refer to this technique as increased relaxation with iron oxide nanoparticles (IRON). Results obtained here show that even at field strengths as high as 4.7 T, one can obtain increases in CNR by factors of 2-3 over BOLD imaging that lead to greater than an order of magnitude increase in statistical power with greatly increased sensitivity to hemodynamic changes in brain regions difficult to observe using BOLD imaging. Furthermore, use of the intravascular contrast agent allows for a meaningful physiologic parameter to be measured (relative cerebral blood volume (rCBV)), compared to conventional BOLD imaging.