title: A numerical investigation of intrathecal isobaric drug dispersion within the cervical subarachnoid space.
abstract: Intrathecal drug and gene vector delivery is a procedure to release a solute within the cerebrospinal fluid. This procedure is currently used in clinical practice and shows promise for treatment of several central nervous system pathologies. However, intrathecal delivery protocols and systems are not yet optimized. The aim of this study was to investigate the effects of injection parameters on solute distribution within the cervical subarachnoid space using a numerical platform. We developed a numerical model based on a patient-specific three dimensional geometry of the cervical subarachnoid space with idealized dorsal and ventral nerve roots and denticulate ligament anatomy. We considered the drug as massless particles within the flow field and with similar properties as the CSF, and we analyzed the effects of anatomy, catheter position, angle and injection flow rate on solute distribution within the cerebrospinal fluid by performing a series of numerical simulations. Results were compared quantitatively in terms of drug peak concentration, spread, accumulation rate and appearance instant over 15 seconds following the injection. Results indicated that solute distribution within the cervical spine was altered by all parameters investigated within the time range analyzed following the injection. The presence of spinal cord nerve roots and denticulate ligaments increased drug spread by 60% compared to simulations without these anatomical features. Catheter position and angle were both found to alter spread rate up to 86%, and catheter flow rate altered drug peak concentration up to 78%. The presented numerical platform fills a first gap towards the realization of a tool to parametrically assess and optimize intrathecal drug and gene vector delivery protocols and systems. Further investigation is needed to analyze drug spread over a longer clinically relevant time frame.
authors.affiliation: Center for Biomedical Computing, Simula Research Laboratory, Fornebu, Norway.
authors.forename: Per Thomas
authors.initials: PT
authors.lastname: Haga
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics, Pontedera, Italy.|Scuola Superiore Sant'Anna, The BioRobotics Institute, Pontedera, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Pizzichelli
authors.affiliation: Center for Biomedical Computing, Simula Research Laboratory, Fornebu, Norway.|Dept. of Mathematics, University of Oslo, Oslo, Norway.
authors.forename: Mikael
authors.initials: M
authors.lastname: Mortensen
authors.affiliation: Dept. of Mathematics, University of Oslo, Oslo, Norway.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Kuchta
authors.affiliation: Conquer Chiari Research Center, Dept. of Mech. Engineering, University of Akron, Akron, Ohio, United States of America.
authors.forename: Soroush Heidari
authors.initials: SH
authors.lastname: Pahlavian
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics, Pontedera, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Sinibaldi
authors.affiliation: Dept. of Biological Engineering, The University of Idaho, Moscow, Idaho, United States of America.
authors.forename: Bryn A
authors.initials: BA
authors.lastname: Martin
authors.affiliation: Center for Biomedical Computing, Simula Research Laboratory, Fornebu, Norway.|Dept. of Mathematics, University of Oslo, Oslo, Norway.
authors.forename: Kent-Andre
authors.initials: KA
authors.lastname: Mardal
mesh_terms: D002574:Cervical Vertebrae; D006801:Humans; D013346:Subarachnoid Space / Q000187:drug effects*