Superparamagnetic NPs embedded Lecithin shell PFP encapsulated microbubble as dual contrast agent for MRI and US

Abstract

Multimodal Imaging is a recent idea for combining two or more imaging methods in synergistic manner to overcome the weakness of individual imaging modalities. The most commonly used imaging techniques in clinic are Ultrasound (US) and Magnetic Resonance Imaging (MRI). As Ultrasound (US) and MRI are complementary techniques so their fusion can overcome the drawbacks of individual imaging. For fully utilizing potential of fusion imaging, dual modal contrast agents are necessary. They help in improving the diagnosis of disease by enhancing contrast resolution as well as can be used for perfusion and functional imaging also reduces the dose thereby reduce the risks, and economic burden of patients. In this study, Oleic acid coated Iron oxide Nanoparticles (OA-IONP) were synthesized via co-precipitation and integrated into shells of Lecithin-Perfluoropentane (PFP) microbubbles using Thin Film Hydration. The magnetic microbubbles were characterized by FTIR, SEM, AFM, MFM, Zeta potential, and contact angle measurements. To investigate the influence of iron oxide NPs concentration on acoustic and magnetic behavior of microbubbles, different Fe concentration (5, 10, 20, 30, 40, 50mg/ml) were used. In-vitro Ultrasound imaging was performed that showed magnetic microbubbles with 10mg IONPs showed 40 times contrast enhancement as compared to control. In-vitro MR Imaging was performed on 0.3 Tesla machine that showed negative contrast enhancement potential of designed construct by producing darker T2 weighted images. The magnetic microbubble with 10 mg IONPs resulted in darker image as compared to water and Gadovist. The signal intensity of magnetic microbubble was 60 which decreases more as the concentration of IONPs in microbubbles increases. The magnetic lecithin microbubble with 10mg IONPs provided better contrast in both Ultrasound and MR imaging. The hemocompatability testing resulted in hemolysis less than 7% with plasma recalcification time and thrombin time of 240s and 6s corresponding to excellent biocompatibility. . Magnetic microbubbles with a liquid PFC gas core encapsulated in a lecithin shell conjugated with Iron oxide NPs can be used as a bimodal contrast agent for both ultrasound and MR imaging, making diagnosis and therapy planning easier.