Convection enhanced delivery to the Brain: preparing for gene therapy and protein delivery to the Brain for functional and restorative Neurosurgery by understanding low-flow neurocatheter infusions using the Alaris® system infusion pump

BACKGROUND Convection enhanced delivery (CED) is an emerging form of direct brain infusion therapy employed in human functional and restorative neurosurgery clinical trials delivering protein, viral vectors for gene therapy, and siRNA. PURPOSE Pressure monitoring has become a vital tool in ensuring infusion safety and success. We report details of this benchmark first trial of the use of a leading syringe infusion pump system capable of low-flow infusions. METHODS Low-flow infusion performance of the FDA approved Alaris® System syringe pump, commonly used at our institution, was assessed during in vitro and ex vivo CED infusions. In vitro infusion cloud morphology and line pressure were analyzed utilizing a neuroinfusion catheter and delivering volumes and flow rates proposed for a human gene therapy protocol for Parkinson's disease. RESULTS Pressure monitoring results correlated with previously published in-line pressure monitoring results however the time to peak with catheter occlusion was extended due to the method of pressure monitoring with this device. CONCLUSION MRI compatible infusion pumps used for brain delivery injectables, pressure monitoring is set to be a guiding instrument for the health care professional employing this emerging form of infusion-to-brain delivery. Further development of infusion pump technology is warranted to allow for infuse/withdraw mode, infusion pressure graphical and numerical display, and pressure monitoring without the need for an inflatable reservoir pressure device. MRI safe infusion systems will need to be available and nursing staff educated to prepare infusions within the high-field environment.