DETERMINANTS OF IN-VIVO MR-IMAGING OF SLOW AXONAL-TRANSPORT

PURPOSE: To investigate specific surface characteristics of magnetic c ontrast agents based on a monocrystalline iron oxide nanoparticle (MIO N) that may determine their uptake and/or transport by axons. MATERIAL S AND METHODS: MION were modified to have a range of surface charges o r 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 correl ated with results at postmortem histologic examination. RESULTS: Subst antial uptake and/or transport by axons occurred only after intraneura l injection and only if the agent had a strong surface charge or was c ovalently linked to WGA. The sciatic nerves appeared as uniformly hypo intense structures having lengths proportional to the time from inject ion to imaging, and the calculated transport rates (4-7 mm/d) were con sistent with slow axonal transport. Numerous Schwann tells and macroph ages acquired large fractions of the injected agents and contributed s ubstantially to the imaging results. CONCLUSION: Those characteristics of MION-based contrast agents that promote efficacy after intraneural injection may impede delivery to the nerve after intraarterial inject ion.