title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, University of Wisconsin, Madison ; BADGER team (Biomedical engineering, Advanced Delivery, and Gene Expression Research team) affiliate, University of Wisconsin, Madison ; Department of Biomedical Engineering, University of Wisconsin, Madison.
authors.forename: Karl
authors.initials: K
authors.lastname: Sillay
authors.affiliation: Department of Neurosurgery, University of Wisconsin, Madison ; BADGER team (Biomedical engineering, Advanced Delivery, and Gene Expression Research team) affiliate, University of Wisconsin, Madison.
authors.forename: Angelica
authors.initials: A
authors.lastname: Hinchman
authors.affiliation: Department of Neurosurgery, University of Wisconsin, Madison ; BADGER team (Biomedical engineering, Advanced Delivery, and Gene Expression Research team) affiliate, University of Wisconsin, Madison.
authors.forename: Erinc
authors.initials: E
authors.lastname: Akture
authors.affiliation: Department of Neurosurgery, University of Wisconsin, Madison ; Department of Pathology and Laboratory, University of Wisconsin, Madison, USA.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Salamat
authors.affiliation: Department of Neurosurgery, University of Wisconsin, Madison ; BADGER team (Biomedical engineering, Advanced Delivery, and Gene Expression Research team) affiliate, University of Wisconsin, Madison.
authors.forename: Gurwattan
authors.initials: G
authors.lastname: Miranpuri
authors.affiliation: Department of Neurosurgery, University of Wisconsin, Madison ; BADGER team (Biomedical engineering, Advanced Delivery, and Gene Expression Research team) affiliate, University of Wisconsin, Madison ; Department of Biomedical Engineering, University of Wisconsin, Madison.
authors.forename: Justin
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Nursing, University of Wisconsin, Madison ; BADGER team (Biomedical engineering, Advanced Delivery, and Gene Expression Research team) affiliate, University of Wisconsin, Madison.
authors.forename: Dawn
authors.initials: D
authors.lastname: Berndt
keywords: Convection enhanced delivery (CED); Functional and restorative neurosurgery; Gene therapy; Infusion therapy; Low-Flow infusions; Neurocatheter infusions; Parkinson’s disease; Pressure monitoring; Real-time MRI monitoring; Syringe pump