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.

Keywords: dual-mode contrast agents; magnetic resonance imaging; medical ultrasound; polymeric microbubbles; superparamagnetic iron oxide nanoparticles.

Figure 1.

TEM images of the three types of CAs. From left to right: (a) cross-sections of MB-plain, (b) MBN-on (SPION weight percentage: 29%) and (c) MBN-into (SPION weight percentage: 15%) are displayed. The black dots represent SPIONs. Note that the cross-sections were obtained at random distances from the equatorial plane of the MBs, resulting in size differences between the analysed MBs. The scale bars represent 500 nm. Courtesy of IOS Press [27].

Figure 2.

Low-field static MRI of the transverse section of four vials containing different CAs. From left to right: MB-plain, MBN-into15, MBN-into38 and MBN-on29.

Figure 3.

Low-field dynamic MRI of the phantom and four CAs. From left to right: MB-plain, MBN-into15, MBN-into38 and MBN-on29.

Figure 4.

Logarithm of the echo amplitude (measured values and regression lines) in static T₂*-weighted MRI as a function of echo time for the four CAs considered.

Figure 5.

Ultrasound images of the phantom with the flow channel filled by different CAs, with different combinations of peak pressure and contrast-specific UI techniques. Peak pressure of: (a) 230 kPa and CPS3, (b) 230 kPa and Chirp CPS3, (c) 320 kPa and CPS3 and (d) 320 kPa and Chirp CPS3. From left to right: MB-plain, MBN-into15, MBN-into38 and MBN-on29.