Molecular MRI of neuroinflammation using a redox-active iron complex

Motivation: Neuroinflammation is a critical pathophysiological process implicated in the development of neurodegenerative disorders. Goal(s): Imaging to detect, monitor, and surveil neuroinflammatory processes could profoundly improve how patients suffering neurodegenerative diseases are diagnosed and managed. Approach: We evaluated brain imaging with the oxidatively activated contrast agent, Fe-PyC3A, as a proxy for inflammatory microglial activity in a mouse model of lipopolysaccharide(LPS)-induced neuroinflammation. Results: Fe-PyC3A generated significantly greater enhancement in LPS-treated mice than in saline-treated controls, correlating with immunohistochemical quantification of microglial activation. Imaging using Gd-DOTA as negative control probe and NOX-2 deficient mice as loss of function control links Fe-PyC3A enhancement with reactive microglial activity. Impact: MRI using oxidatively activated probes as a potential marker to detect and quantify neuroinflammatory processes could profoundly improve how patients suffering neurodegenerative diseases are diagnosed and managed.