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.
Highlights
Dual-mode contrast agents (CAs) have great potential for improving diagnostics
We focus on magnetic resonance imaging (MRI)/ultrasound imaging (UI) dual-mode CAs assembled by combining polymer-shelled MBs and superparamagnetic iron oxide nanoparticles (SPIONs) according to two recently proposed strategies [7]
Acoustic characterization of magnetic MBs demonstrated that the dependence of backscattered power on the MB concentration is complex [19]: when the concentration was increased, saturation of the backscattered power was observed for MBs with embedded SPIONs (MBN-into) starting from 2 × 106 MBs ml−1, whereas a backscattered power decrease was observed for MBs coated with SPIONs (MBN-on) starting from 106 MBs ml−1
Summary
Dual-mode contrast agents (CAs) have great potential for improving diagnostics. 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. Imaging techniques often require specific contrast agents (CAs) to improve lesion and tissue characterization, anatomical visualization of body structures, morphological assessment, blood pool enhancement and perfusion imaging Owing to these combined advantages, the development of dualmode or multi-modal CAs is a useful way to obtain more valuable diagnostic information and to achieve more valuable treatment solutions [3]. Dual-mode agents for UI and MRI [4,5,6,7,8,9] that potentially combine the advantages of those two imaging techniques, or the high temporal resolution of UI and the high spatial resolution of MRI, have been proposed For this type of CA, micro-devices and nanoparticles are used jointly: ultrasound CAs, composed of gas-filled microbubbles (MBs) protected by a shell [10], are complemented with nanoparticles (e.g. metal oxide, metal or semiconductor particles) that provide the desired magnetic response. Alternative solutions based on polymeric nanocapsules with a liquid perfluorooctyl bromide core [3,14] or a perfluorocarbon nanoparticle emulsion [15] have been proposed to develop MRI/UI dual-mode CAs, even if the solid, incompressible nanoparticles significantly reduce the ultrasound backscattering efficiency (i.e. the CAs’ echogenicity) [16,17]
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