Highly Sensitive Diagnosis of Extracellular Calcium Ions Associated Brain Diseases using Ca2+-Dependent T2-T1 Switchable Magnetic Nanosensors

Calcium ions (Ca 2+ ) play crucial roles as second messengers in living cells and are associated with the onset and development of chronic brain diseases, including epilepsy. Dynamic and real-time imaging of extracellular calcium levels ([Ca 2+ ] ex ) in the brain holds great potential for identifying disease foci. Magnetic resonance imaging (MRI) is a powerful non-invasive tool for Ca 2+ imaging with unlimited depth penetration. However, current available Ca 2+ MR sensors lack the sensitivity to monitor small [Ca 2+ ] ex alterations associated with chronic brain diseases in vivo. In this study, a highly sensitive Ca 2+ -dependent T2-T1 switchable magnetic nanosensor is reported, consisting of Ca 2+ -specific ligands engineered near-paramagnetic iron oxide nanoparticles. Surface ligand modifications can be adjusted to regulate the interaction energy between sensors and Ca 2+ , allowing for customizable response range and sensitivity to fulfill the in vivo imaging requirements. The optimized sensors enable non-invasive visualization of early-stage seizure focus in mice undergoing epilepsy.