In vivo contrast-enhanced MR imaging of direct infusion into rat peripheral nerves

Direct infusion, or convection-enhanced delivery (CED), into peripheral nerves may provide a method for delivering substances to the intrathecal space or specific fiber bundles entering the spinal cord. To better understand this potential delivery technique, we have characterized the extracellular transport of macromolecular agents from peripheral nerves to the spinal cord in magnetic resonance (MR) imaging studies. High-resolution dynamic contrast-enhanced MR imaging at 11.1 T was used to monitor and characterize in vivo the extracellular transport dynamics of Gd-DTPA-albumin tracer during CED into rat sciatic nerves. Extracellular tracers followed peripheral nerves towards the spinal cord and at vertebral levels L4 and L5 appeared to enter the cerebrospinal fluid and nerve roots. Uptake directly into spinal cord tissues (white and gray matter) appeared to be limited. Spatial distribution patterns within spinal cord regions depended on CED factors, including cannula placement, and underlying tissue structures including peripheral nerve branching and membrane structures at nerve root entry. The applied MR techniques allowed for visualization and quantification of tracer spread and distribution within the rat spinal cord region. The results show that CED into peripheral nerves provides an alternative route for delivering therapeutics to nerve roots and the intrathecal space surrounding the spinal cord.