In vivo magnetic resonance imaging of endogenous neuroblasts labelled with a ferumoxide–polycation complex

Abstract

Neurogenesis occurs at the subependymal zone (SEZ) of the adult brain. Neural progenitor cells give rise to neuroblasts, which migrate to the olfactory bulb (OB) via the rostral migratory stream (RMS). Development of methods capable of labelling and tracking these cells in vivo would be of great benefit to the understanding of neuroblast migration away from the SEZ under normal and pathological conditions. In this study, we demonstrate that endogenous neuroblasts can be labelled in vivo with an MRI contrast agent and that they can be visualised using MRI. We compared two labelling strategies: intraventricular injection of the ferumoxide Endorem, with or without the transfection agent protamine sulphate. Administration of Endorem alone resulted in its distribution outside of the ventricle and into the periventricular space after 48 h. In contrast, we observed that intraventricular injection of Endorem complexed to protamine sulphate – forming the FePro complex – is restricted to the ventricular walls after 48 h. The FePro complex successfully labelled Doublecortin + neuroblasts in vivo up to 28 days post-injection. FePro-labelled neuroblasts in the RMS could be visualised using MRI in vivo and ex vivo on a 2.35 T MRI system, and FePro-labelled cells were identified in the OB on a 9.4 T MRI system. This study demonstrates the feasibility of in vivo imaging of endogenous neuroblast migration using MRI.