F-19 magnetic resonance imaging (MRI) is a powerful noninvasive imaging technique with demonstrated potential for the detection of important diseases. The major challenge in the design of F-19 MRI agents is signal attenuation caused by the reduced solubility and segmental mobility of probes with high numbers of fluorine atoms. Careful choice of the fluorinated moiety is required to maintain image quality at the fluorine contents required for high imaging: sensitivity. Here we report the synthesiS of perfluoropolyether (PFPE) end-functionalized homopolytners of oligo(ethylene glycol) methyl ether acrylate (poly(OBGA)(m)-PFPE) as highly sensitive F-19 MRI contrast agents (CAs). The structural characteristics, conformation and aggregation behavior; F-19 NMR relaxation properties, and F-19 MR imaging were studied in detail. Dynamic light scattering and molecular dynamics (MD) simulations were,conducted and demonstrated,that poly(OEGA)(m)-PFPB with the longest poly(OEGA)(m) segments (m = 20) undergoes single-chain folding in water while poly(OEGA)(10)-PFPE and poly(OEGA)(4)-PFPE with shorter OEGA segments experience multiple-chain aggregation. Long F-19 T-2 relaxation times were measured for all poly(OEGA)(m)-PFPE polymers in PBS and in the presence of Serum (>80 ms), and no obvious decrease in F-19 T-2 was, observed with increasing fluorine content up to similar to 30 wt %. Moreover, the signal-to-noise ratio increased linearly with increasing concentration of fluorine, indicating that the PFPE-based polymers can be applied as quantitative tracers. Furthermore, we investigated the in vivo behavior, in particular their biodistribution, of the polymers with different aggregation properties. Control over the balance of hydrophobicity and hydrophilicity allows manipulation of the aggregation state, and this leads to different circulation behavior in a murine model. This first report of the synthesis of polymeric PFPE-based F-19 MRI CAs demonstrates that these polymers are an exciting new class, of F-19 MRI CAs with extremely high fluorine content and outstanding imaging sensitivity.