(156a) Gadolinium-Bound Microbubble Shells for MRI Biosensors

Gas filled microbubbles have potential applications for MRI-guided focused ultrasound (MRIg-FUS) therapy. These microbubbles are being used as contrast agents for Ultrasound imaging and targeted drug delivery due to their compressible gas cores that provides a strong backscatter echo that can be detected by the transducer at lower acoustic pressures. Furthermore, techniques like Sonoporation allow for localized delivery of microbubble shell material and increased permeability of targeted cellular regions. Recently preformed microbubbles have been applied in combination with focused ultrasound to transiently and noninvasively open the Blood-Brain-Barrier (BBB) allowing for delivery of drugs that treat neurodegenerative disorders such as Parkinson’s and Alzheimer’s. These microbubbles lowered the acoustic intensity threshold needed for BBB opening. The opening and closing of the BBB was determined by monitoring the signal intensity of an MRI contrast agent in the targeted region over time. However, the mechanism of microbubble mediated blood brain barrier opening was not fully understood.  To help elucidate the mechanism, microbubbles shells containing the MRI contrast agent, Gadolinium (Gd) were designed using post-labeling techniques. Characterization of the novel Gd-bound microbubbles resulted in an unexpected observation, wherein the MRI signal intensity increased only after fragmentation of the initial monolayer gas-containing construct by ultrasound to produce bilayer vesicles. This inherent nature of microbubbles provides the opportunity to utilize them as ultrasound triggered MRI contrast agents. The MRI signal can be spatially and temporally controlled via microbubble destruction by external acoustic forces, since the negative contrast should go away with absence of gas-liquid interface and the positive contrast provided by the Gd, which remain present with the lipid shell, should increase due to presence of paramagnetic contrast agent (CA) on the remnant shell material.  Therefore, the novel Gd-bound microbubble provides a means of detecting the location and intensity of ultrasound-induced microbubble destruction during MRIg-FUS therapy.  The construct is expected to improve the monitoring and reduce the negative side effects of MRI-guided high intensity focused ultrasound therapy.