Calcium-dependent molecular fMRI using a magnetic nanosensor

Calcium ions are ubiquitous signaling molecules in all multicellular organisms, where they mediate diverse aspects of intracellular and extracellular communication over widely varying temporal and spatial scales(1). Although techniques for mapping calcium-related activity at high resolution by optical means are well established, there is currently no reliable method to measure calcium dynamics over large volumes in intact tissue(2). Here we address this need by introducing a family of magnetic calcium-responsive nanoparticles (MaCaReNas) that can be detected by magnetic resonance imaging (MRI). MaCaReNas respond within seconds to [Ca(2+)] changes in the 0.1-1.0 mM range, suitable for monitoring extracellular calcium signaling processes in the brain. We show that the probes permit repeated detection of brain activation in response to diverse stimuli in vivo. MaCaReNas thus provide a tool for calcium activity mapping in deep tissue and offer a precedent for development of further nanoparticle-based sensors for dynamic molecular imaging with MRI.