The authors suggest that ultra-small paramagnetic iron oxide (USPIO) particles used as blood pool contrast agents may increase the sensitivity of midfield MRI (i.e., less than 1.5 Tesla) to physiological variations in cerebral blood volume. This hypothesis was tested on a rabbit model of apnea which increases pCO2 and cerebral blood volume. Using Sinerern as the USPIO at a blood concentration of 60 mumol Iron/kg body weight, an 8% T2*-weighted signal decrease could be observed at 1.0 T with 25-33% increase in pCO2. Comparatively, in the absence of USPIO, T2*-weighted signal dropped only 4% during apnea and after mild hyperoxygenation beforehand, due to increased deoxyhemoglobin content. These preliminary data suggest that USPIOs could play an important role in functional MRI at midfield strength, by sensitizing the signal to cerebral blood volume changes.