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Magnetic Resonance Detection of Gas Microbubbles via HyperCEST: A Path Toward Dual Modality Contrast Agent
Authors:Christian T. McHugh  Phillip G. Durham  Michele Kelley  Prof. Paul A. Dayton  Prof. Rosa T. Branca
Affiliation:1. Department of Physics & Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA;2. Department of Pharmacoengineering and Molecular Pharmaceutics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA;3. Department of Physics & Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA

Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA;4. Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA

Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA

Abstract:Gas microbubbles are an established clinical ultrasound contrast agent. They could also become a powerful magnetic resonance (MR) intravascular contrast agent, but their low susceptibility-induced contrast requires high circulating concentrations or the addition of exogenous paramagnetic nanoparticles for MR detection. In order to detect clinical in vivo concentrations of raw microbubbles via MR, an alternative detection scheme must be used. HyperCEST is an NMR technique capable of indirectly detecting signals from very dilute molecules (concentrations well below the NMR detection threshold) that exchange hyperpolarized 129Xe. Here, we use quantitative hyperCEST to show that microbubbles are very efficient hyperCEST agents. They can accommodate and saturate millions of 129Xe atoms at a time, allowing for their indirect detection at concentrations as low as 10 femtomolar. The increased MR sensitivity to microbubbles achieved via hyperCEST can bridge the gap for microbubbles to become a dual modality contrast agent.
Keywords:biosensors  hyperCEST  microbubbles  NMR spectroscopy  xenon
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