Calcium ions are central to signal transduction within cells. They coordinate biological processes ranging from embryonic development to neural function. Being able to detect calcium flux within tissues is essential to the accurate evaluation of cellular activity. However, current methods to measure calcium flux within live tissues for clinical diagnostics remains a challenge. While optical probes for intracellular calcium imaging exist, current strategies to monitor intracellular calcium signaling for clinical applications require invasive surgery to achieve greater tissue penetration. Moreover, attempts to achieve optimal tissue penetration noninvasively forgo image resolution. Magnetic resonance imaging (MRI) is a powerful technique that can provide the basis for deep-tissue calcium imaging in humans and animals. This invention presents a strategy for real-time monitoring of intracellular calcium levels with functional magnetic resonance imaging using novel manganese-based paramagnetic contrast agents which sense calcium.