A preparation of ultra-small superparamagnetic iron oxide (USPIO) particles coupled to an RGD peptide (RGD-USPIO) was investigated as an MR contrast agent, targeted to activated platelets, in both ex vivo and in vivo thrombus models. Thrombus visualization ex vivo was compared using RGD-USPIO and a non-targeted UPSIO. The influence of thrombus visualization on thrombus exposure time to RGD-USPIO (ex vivo) and on the spatial resolution of the MR image (ex vivo and in vivo) was assessed. RGD-USPIO resulted in better thrombus visualization than non-targeted USPIO ex vivo, and maximum enhancement was achieved after approximately one hour exposure time of the thrombus to RGD-USPIO. The ability to visualize the clots was highly dependent on the spatial resolution of the image. In vivo, an in-plane resolution of less than 0.2 x 0.2 mm(2) was required for good clot visualization after contrast enhancement. It is concluded that the achievable resolution and sensitivity is a potential limitation to the usefulness of active vascular targeting in MRI.