Ultrasound detection of nanoparticle contrast agents for multimodal molecular imaging

Aim of the present work was, first, to demonstrate feasibility and usefulness of subharmonic imaging of silica nanospheres (SiNSs) at diagnostic ultrasound (US) frequencies and, second, to investigate the acoustic effectiveness of a new class of multimodal nanocomposite contrast agents, towards dual mode investigations combining US and magnetic resonance imaging (MRI). We employed SiNSs of variable diameter (160 nm, 330 nm and 660 nm) dispersed in different volume concentrations (range 0.07-0.8%) in agarose gel samples that were automatically scanned through a digital ecograph using narrow-band US pulses, varying both frequency (range 5-10 MHz) and mechanical index (MI range 0.2-0.6). Raw radiofrequency data were acquired and off-line processed, in order to study the behaviour of fundamental and subharmonic component as a function of incident frequency, MI, SiNS size and concentration. The experiments were also repeated on different agarose samples, containing SiNSs covered by an outer shell of smaller magnetic nanoparticles, made of either iron oxide (FeO) or FePt-FeO nanocrystals. Obtained results show that the highest sensitivity of subharmonic intensity to nanoparticle presence was always found for 330-nm SiNSs, that can be effectively detected at very low volume concentrations (0.07%) by employing a low MI (0.2). These properties were maintained by SiNSs even after a coverage by an outer magnetic shell, so representing a valuable candidate for tasks of dual mode molecular imaging.