Contrast-enhanced Functional Blood Volume Imaging (CE-fBVI): Enhanced Sensitivity for Brain Activation in Humans Using the Ultrasmall Superparamagnetic Iron Oxide Agent Ferumoxytol

Neuroimage. 2012 Sep;62(3):1726-31. doi: 10.1016/j.neuroimage.2012.05.010. Epub 2012 May 11.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Volume / physiology
  • Blood Volume Determination / methods*
  • Brain / physiology*
  • Brain Mapping / methods*
  • Contrast Media*
  • Ferrosoferric Oxide*
  • Humans
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Psychomotor Performance / physiology
  • Signal-To-Noise Ratio
  • Young Adult


  • Contrast Media
  • Ferrosoferric Oxide