MRI detection of single particles for cellular imaging

TLDR

MRI is increasingly used for molecular and cellular imaging, but current approaches rely on loading millions of ultrasmall dextran‑coated iron oxide particles into cells to achieve sufficient relaxivity. This study demonstrates that single micrometer‑sized iron oxide particles (MPIOs) can be detected by MRI in vitro, in cultured cells, and in mouse embryos. Cells were labeled with fluorescent MPIOs so that each cell contained a single particle, enabling simultaneous MRI and fluorescence imaging. Single MPIOs produced detectable T2* effects at 50‑µm resolution (and down to 200 µm), were visualized by MRI and fluorescence in individual cells, and remained detectable in mouse embryos after many cell divisions, confirming MRI’s capability for single‑particle cellular imaging.

Abstract

There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 microm indicated that T(2)* effects can be readily detected from single MPIOs at 50-microm resolution and significant signal effects could be detected at resolutions as low as 200 microm. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging.