Manganese-enhanced gene expression MRI using Zip14

Motivation: Zip14 is an in vivo MRI-visible gene expression reporter system capable of producing focal signal changes without administration of additional contrast agents. However, it is not yet known how much contrast-enhanced MRI will improve sensitivity for Zip14 expression. Goal(s): Our goal was to understand how systemically delivered manganese (Mn2+)-enhanced MRI (MEMRI) would improve Zip14 contrast. Approach: Zip14 was expressed in the mouse brain and MRI was performed as previously described. MnCl2 was injected intraperitoneally and MEMRI was performed. Results: MEMRI improved Zip14 contrast by approximately four-fold at the injection site, by two-fold at sites of anterograde tracing, and revealed previously undetectable tracing sites. Impact: Although supplemental Mn2+ is not required to observe T1-weighted MRI signal enhancement produced by Zip14 expression, it can significantly improve contrast. Increased sensitivity for Zip14 expression with MEMRI will improve measurement of neural connectivity, degeneration, and plasticity in vivo.