A Calcium-Sensitive Magnetic Resonance Imaging Contrast Agent

Ca^(2+) is an important intracellular secondary messenger of signal transduction. Changes in the cytosolic concentration of Ca^(2+) trigger changes in cellular metabolism and are responsible for cell signaling and regulation. Advances in optical microscopy techniques and improvements in fluorescent dyes capable of measuring Ca^(2+) concentration have added greatly to the understanding of the critical role this ion plays in cell and neurobiology. However, a fundamental limitation of light-based microscope imaging techniques employing dyes or fluorochromes is that they produce toxic photobleaching byproducts and are limited by light scattering to those cells within 100 µm of the surface. Magnetic resonance imaging (MRI) of biological structures provides an alternative to light-based microscopy that can circumvent these limitations. Recent work in this area has demonstrated the feasibility of true three-dimensional MR imaging at cellular resolution (~10 µm).