title: The effect of pulsatile flow on intrathecal drug delivery in the spinal canal.
abstract: Clinical studies have shown that drugs delivered intrathecally distribute much faster than can be accounted for by pure molecular diffusion. However, drug transport inside the cerebrospinal fluid (CSF)-filled spinal canal is poorly understood. In this study, comprehensive experimental and computational studies were conducted to quantify the effect of pulsatile CSF flow on the accelerated drug dispersion in the spinal canal. Infusion tests with a radionucleotide and fluorescent dye under stagnant and pulsatile flow conditions were conducted inside an experimental surrogate model of the human spinal canal. The tracer distributions were quantified optically and by single photon emission computed tomography (SPECT). The experimental results show that CSF flow oscillations substantially enhance fluorescent dye and radionucleotide dispersion in the spinal canal experiment. The experimental observations were interpreted by rigorous computer simulations. To demonstrate the clinical significance, the dispersion of intrathecally infused baclofen, an anti-spasticity drug, was predicted by using patient-specific spinal data and CSF flow measurements. The computational predictions are expected to enable the rational design of intrathecal drug therapies.
authors.affiliation: Laboratory for Product and Process Design, Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: H D M
authors.initials: HD
authors.lastname: Hettiarachchi
authors.forename: Ying
authors.initials: Y
authors.lastname: Hsu
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Harris
authors.forename: Richard
authors.initials: R
authors.lastname: Penn
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Linninger
mesh_terms: D000465:Algorithms; D001418:Baclofen / Q000008:administration & dosage / Q000493:pharmacokinetics; D002555:Cerebrospinal Fluid / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D007278:Injections, Spinal; D008954:Models, Biological; D009128:Muscle Spasticity / Q000188:drug therapy; D011673:Pulsatile Flow / Q000502:physiology*; D013115:Spinal Canal / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D001418:Baclofen