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

Abstract

Dual-mode contrast agents (CAs) have great potential for improving diagnostics. However, the effectiveness of CAs is strictly related to both the solution adopted to merge the two agents into a single probe unit, and the ratio between the two agents. In this study, two dual-mode CAs for simultaneous magnetic resonance imaging (MRI) and ultrasound imaging (UI) were assessed. For this purpose, different densities of superparamagnetic iron oxide nanoparticles (SPIONs) were anchored to the external surface of polymer-shelled microbubbles (MBs) or were physically entrapped into the shell. In vitro static and dynamic experiments were carried out with a limited concentration of modified MBs (106 bubbles ml−1) by avoiding destruction during UI (performed at a peak pressure lower than 320 kPa) and by using a low-field MRI system (with a magnetic flux density equal to 0.25 T). Under these conditions, different imaging techniques, set-up parameters and SPION densities were used to achieve satisfactory detection of the CAs by using both UI and MRI. However, when the SPION density was increased, the MRI contrast improved, whereas the UI contrast worsened due to the reduced elasticity of the MB shell. For both UI and MRI, MBs with externally anchored SPIONs provided better performance than MBs with SPIONs entrapped into the shell. In particular, a SPION density of 29% with respect to the mass of the MBs was successfully tested.

Cellular Uptake of Plain and SPION-Modified Microbubbles for Potential Use in Molecular Imaging

“…fully characterizing the US and MR imaging properties of these bubbles was published. 53 Micro-devices similar to these have also been identified useful within fields as imaging and theranostics and are reported recently. 8 , 56 , 64 …”

Microbubbles containing gadolinium as contrast agents for both phase contrast and magnetic resonance imaging

“…Portal vein imaging is commonly performed using these imaging techniques. However, each of these imaging modalities has its own advantages and limitations in areas such as resolution, sensitivity, scanning speed and penetration depth (Sciallero et al, 2016;Gregg & Butcher, 2012;Chiriacò et al, 2013). Considerable improvement can be obtained by combining two or more imaging techniques simultaneously.…”

Multiplexed imaging for diagnosis and therapy

“…Nanoscale and microscale hybrid US-MRI probes almost exclusively build on previously successful single-modality nanoparticle and lanthanidechelate probes for MRI and on microbubble schemes for US. The modular design of these probes facilitates fusion of magnetic-and ultrasound-contrast enhancing properties into dual-modality probes for US-MRI with tuneable physical and pharmacokinetic properties [87][88][89][90][91] . The most notable applications of US-MRI for therapy include sonoporation (using microbubbles for gene or drug delivery) and MR-guided high-intensity focused ultrasound (MR-HIFU; used for image-guided thermal ablation 92,93 ).…”

“…Parallel paths of innovation in US and nanomedicine have spurred the development of a host of techniques in therapeutics, including focused-US-induced drug release and MR-guided drug delivery 88,91,213,[226][227][228] , such as chemotherapy of lymph-node metastasis in rabbits following MR/US-guided release of doxorubicin encapsulated within superparamagnetic microbubbles 228 .…”