Determinants of in vivo MR imaging of slow axonal transport.

Abstract

To investigate specific surface characteristics of magnetic contrast agents based on a monocrystalline iron oxide nanoparticle (MION) that may determine their uptake and/or transport by axons. MION were modified to have a range of surface charges or were covalently linked to wheat germ agglutinin (WGA), a neurotropic protein. Each agent was injected directly into the sciatic nerves or femoral arteries of rats (n = 22), and magnetic resonance (MR) images were obtained several days later. The imaging results then were correlated with results at postmortem histologic examination. Substantial uptake and/or transport by axons occurred only after intraneural injection and only if the agent had a strong surface charge or was covalently linked to WGA. The sciatic nerves appeared as uniformly hypointense structures having lengths proportional to the time from injection to imaging, and the calculated transport rates (4-7 mm/d) were consistent with slow axonal transport. Numerous Schwann cells and macrophages acquired large fractions of the injected agents and contributed substantially to the imaging results. Those characteristics of MION-based contrast agents that promote efficacy after intraneural injection may impede delivery to the nerve after intraarterial injection.