We have previously reported molecular MRI studies using Microparticles of Iron Oxide (MPIO) coupled to anti-VCAM-1 antibodies. However, Ultrasmall Superparamagnetic Iron Oxide (USPIO) are more commonly used in MRI applications. Although MPIO provide greater targeting valency and contrast per particle, their advantages over UPSIO for molecular MRI has not been demonstrated empirically. Here, we compared the sensitivity and specificity of VCAM-MPIO and VCAM-USPIO for molecular MRI; VCAM-MPIO, but not VCAM-USPIO, yielded marked and selective contrast in areas of cerebral inflammation. These results confirm the theoretical assumption that MPIO present a more viable platform for molecular MRI than USPIO.