Fast screening of paramagnetic molecules in zebrafish embryos by MRI

Zebrafish embryo is a well-established model used in many fields of modern experimental biology. We demonstrate that it provides a promising model platform for exploring fundamental MR aspects that can be used to screen and study active MR molecules before progressing to more complex living systems. Setting up a dedicated MRI methodology, we arrayed a large number of living embryos, which were microinjected at very early stages of development with different contrast agents. We also showed that MRI signal intensity correlates with the gadolinium content of zebrafish embryos. This allowed us to validate a new approach for MR compound screening. Using a specific surface coil of 5 mm inner diameter, we obtained for the first time high-spatial-resolution images at 7 T of living zebrafish embryos with a 47 microm isotropic voxel size with an acquisition time of 39 min. Finally, we discuss potential applications of this development: a viable in vivo assay for screening small pharmacological compounds; assessment of and tracking the action of molecules over time. Exploring in vivo biological activity, gene function analysis, and detailed characterization of disease processes in fish are natural extensions of these preliminary studies.