Contrast-enhanced functional blood volume imaging (CE-fBVI): Enhanced sensitivity for brain activation in humans using the ultrasmall superparamagnetic iron oxide agent ferumoxytol

Functional MRI (fMRI) brain studies performed in the presence of a steady-state or “blood pool” contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise ratio (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional blood volume imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood-oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8 ± 1.3 s) and a slow (75.3 ± 27.5 s) component of CBV response to stimuli. A significant CNR gain of approximately 2-3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping.

► First report of the use of USPIO for functional brain activation in humans. ► The method is sensitive to blood volume changes and is termed CE-fBVI. ► A significant CNR gain of about 2-3 was found for CE-fBVI compared to BOLD fMRI. ► Less susceptibility-related signal dropout was found with CE-fBVI. ► Time response of CE-fBVI to stimuli was characterized.