title: In vivo performance of a microfabricated catheter for intraparenchymal delivery.
abstract: BACKGROUND
  Convection-enhanced delivery (CED) is currently the only effective clinical technique to deliver biological therapeutic agents that would otherwise not cross the blood-brain barrier. Despite the promise of CED, several technical problems have limited its effectiveness.
  
  
  METHODS
  Brain infusions into a large mammal (pig) were performed with a catheter that was fabricated using micro-electro-mechanical systems (MEMS) technology (Olbricht et al., 2010). The performance of the catheter was evaluated for infusions at increasing infusion rates. Magnetic resonance (MR) images were acquired in real time to examine the distribution of infused tracers in the parenchyma.
  
  
  RESULTS
  Both backflow and the distribution of CED of infusates into a variety of cytoarchitectures in porcine brain were quantified. Concentration profiles were determined for several MR contrast reagents as well as a fluorescent dye that are the sizes of small molecules, therapeutic proteins and an adeno-associated virus (AAV). The reagents can serve as surrogates for assessing the convective distribution of active molecules. Infusion rates up to 20μL/min were attained without evidence of backflow along the catheter.
  
  
  METHODS
  The device performed well in terms of both backflow and infusion, superior to that of many studies reported in the literature on other catheters. All infused molecules had comparable ratios of distribution to infusion volumes.
  
  
  CONCLUSIONS
  The catheter described in this report appears able to target tissue structures with precision, deliver therapeutics at high infusion rates, and resist backflow that can compromise the efficacy of CED therapy. The technology allows development of "smart" catheters for future applications.
authors.affiliation: Therataxis, LLC, Baltimore, MD, United States.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Brady
authors.affiliation: Therataxis, LLC, Baltimore, MD, United States. Electronic address: raghu@therataxis.com.
authors.forename: Raghu
authors.initials: R
authors.lastname: Raghavan
authors.affiliation: Alcyone Lifesciences, Inc, Concord, MA, United States.
authors.forename: Deep
authors.initials: D
authors.lastname: Singh
authors.affiliation: Alcyone Lifesciences, Inc, Concord, MA, United States.
authors.forename: P J
authors.initials: PJ
authors.lastname: Anand
authors.affiliation: Alcyone Lifesciences, Inc, Concord, MA, United States; Banner Alzheimer's Institute, Phoenix, AZ, United States.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA, United States.
authors.forename: Jaime
authors.initials: J
authors.lastname: Mata
authors.affiliation: Department of Neurosurgery, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: William C
authors.initials: WC
authors.lastname: Broaddus
authors.affiliation: School of Chemical and Biomolecular Engineering and Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, United States.
authors.forename: William L
authors.initials: WL
authors.lastname: Olbricht
mesh_terms: D000818:Animals; D001921:Brain; D057785:Catheters; D002533:Cerebral Angiography; D003287:Contrast Media / Q000008:administration & dosage; D056324:Diffusion Tensor Imaging; D004867:Equipment Design; D005456:Fluorescent Dyes / Q000008:administration & dosage; D007263:Infusions, Parenteral / Q000295:instrumentation*; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D055616:Microtechnology; D010316:Particle Size; D011312:Pressure; D011699:Putamen; D013552:Swine; D013788:Thalamus; D066127:White Matter
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes
keywords: Alcyone microcatheter; Convection-enhanced delivery; In vivo infusions; Microfabricated catheter; Parkinson's disease; Porcine model