Gas vesicles: Acoustic biomolecules for ultrasound imaging

Abstract

Expanding the capabilities of ultrasound for biological and diagnostic imaging requires the development of contrast agents linked to cellular and molecular processes in vivo. In optical imaging this is commonly accomplished using fluorescent biomolecules such as the green fluorescent protein. Analogously, we recently introduced gas vesicles (GVs) as the first acoustic biomolecules for ultrasound. GVs are physically stable gas-filled protein nanostructures (~250 nm) naturally expressed in aquatic photosynthetic microbes as a means to regulate buoyancy. Purified GVs produce robust ultrasound contrast across a range of frequencies at picomolar concentrations, exhibit nonlinear scattering to enable enhanced detection versus background in vivo, and have species-dependent thresholds for pressure-induced collapse to enable multiplexed imaging. Here, I will present our recent progress on understanding the biophysical and acoustic properties of these biomolecular contrast agents, engineering their mechanics and targeting at the genetic level, developing ultrasound pulse sequences to enhance their detection in vivo and expressing them heterologously as acoustic reporter genes. 1. Shapiro, M.G. et al. Nat. Nanotechnol. 9, 311-316 (2014). 2. Cherin, M. et al. U.M.B. (In press). 3. Lakshmanan, A. et al. ACS Nano 10, 7314-7322 (2016). 4. Maresca, D. et al. In revision. 5. Bourdeau, R.W. et al. Submitted. More information at http://shapirolab.caltech.edu.

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