Magnetic resonance and ultrasound contrast imaging of polymer-shelled microbubbles loaded with iron oxide nanoparticles

Dual-mode contrast agents (CAs) have great potential forimproving diagnostics. However, the effectiveness of CAs isstrictly related to both the solution adopted to merge the twoagents into a single probe unit, and the ratio between the twoagents. In this study, two dual-mode CAs for simultaneousmagnetic resonance imaging (MRI) and ultrasound imaging(UI) were assessed. For this purpose, different densitiesof superparamagnetic iron oxide nanoparticles (SPIONs)were anchored to the external surface of polymer-shelledmicrobubbles (MBs) or were physically entrapped into theshell.In vitrostatic and dynamic experiments were carriedout with a limited concentration of modified MBs (106bubblesml−1) by avoiding destruction during UI (performed at apeak pressure lower than 320 kPa) and by using a low-field MRI system (with a magnetic flux density equal to0.25 T). Under these conditions, different imaging techniques,set-up parameters and SPION densities were used to achievesatisfactory detection of the CAs by using both UI and MRI.However, when the SPION density was increased, the MRIcontrast improved, whereas the UI contrast worsened dueto the reduced elasticity of the MB shell. For both UI andMRI, MBs with externally anchored SPIONs provided betterperformance than MBs with SPIONs entrapped into the shell.In particular, a SPION density of 29% with respect to the massof the MBs was successfully tested. Magnetic resonance and ultrasound contrast imaging of polymer-shelled microbubbles loaded with iron oxide nanoparticles