{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:31:15Z","timestamp":1772209875451,"version":"3.50.1"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there was a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with cervical implantation compared to lumbar implantation. CSF flow rate decreased up to 55% with the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation in Cynomolgus monkeys.<\/jats:p>","DOI":"10.1371\/journal.pone.0244090","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T14:37:40Z","timestamp":1609339060000},"page":"e0244090","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys"],"prefix":"10.1371","volume":"15","author":[{"given":"Mohammadreza","family":"Khani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey Q.","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Pluid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina P.","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John N.","family":"Oshinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory R.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillynne R.","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1234-7880","authenticated-orcid":true,"given":"Bryn A.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,30]]},"reference":[{"issue":"5","key":"pone.0244090.ref001","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1177\/1049909111426134","article-title":"Intrathecal drug delivery system (IDDS) for cancer pain management: a review and updates.","volume":"29","author":"SP Upadhyay","year":"2012","journal-title":"Am J Hosp Palliat Care"},{"issue":"3","key":"pone.0244090.ref002","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1227\/01.NEU.0000227570.40402.77","article-title":"Cervical catheter tip placement for intrathecal baclofen administration.","volume":"59","author":"TD McCall","year":"2006","journal-title":"Neurosurgery"},{"issue":"1","key":"pone.0244090.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JND-190424","article-title":"Advances in Treatment of Spinal Muscular Atrophy\u2014New Phenotypes, New Challenges, New Implications for Care.","volume":"7","author":"DC Schorling","year":"2020","journal-title":"J Neuromuscul Dis."},{"issue":"2","key":"pone.0244090.ref004","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s10549-019-05317-6","article-title":"Breast leptomeningeal disease: a review of current practices and updates on management","volume":"177","author":"NB Figura","year":"2019","journal-title":"Breast Cancer Res Treat"},{"issue":"1","key":"pone.0244090.ref005","first-page":"vdaa052","article-title":"Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases.","volume":"2","author":"T Ejikeme","year":"2020","journal-title":"Neurooncol Adv."},{"key":"pone.0244090.ref006","article-title":"Impact of Neurapheresis system on intrathecal cerebrospinal fluid dynamics: a computational fluid dynamics study","author":"M Khani","year":"2019","journal-title":"J Biomech Eng"},{"issue":"7","key":"pone.0244090.ref007","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/infdis\/jiy286","article-title":"Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy","volume":"218","author":"GJ Smilnak","year":"2018","journal-title":"J Infect Dis"},{"key":"pone.0244090.ref008","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1017\/jfm.2018.67","article-title":"On the bulk motion of the cerebrospinal fluid in the spinal canal","volume":"841","author":"AL Sanchez","year":"2018","journal-title":"Journal of Fluid Mechanics"},{"issue":"4","key":"pone.0244090.ref009","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1109\/TBME.2019.2930451","article-title":"In Vivo Intrathecal Tracer Dispersion in Cynomolgus Monkey Validates Wide Biodistribution Along Neuraxis","volume":"67","author":"K Tangen","year":"2020","journal-title":"IEEE Trans Biomed Eng"},{"issue":"1","key":"pone.0244090.ref010","first-page":"10","volume":"11","author":"T Brinker","year":"2014","journal-title":"CNS Bot. A new look at cerebrospinal fluid circulation"},{"issue":"1","key":"pone.0244090.ref011","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12987-019-0164-3","article-title":"Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients.","volume":"17","author":"LR Sass","year":"2020","journal-title":"Fluids Barriers CNS."},{"issue":"7","key":"pone.0244090.ref012","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/00004424-200107000-00003","article-title":"Cerebrospinal fluid dynamics and relation with blood flow\u2014A magnetic resonance study with semiautomated cerebrospinal fluid segmentation","volume":"36","author":"O Baledent","year":"2001","journal-title":"Investigative Radiology"},{"issue":"1","key":"pone.0244090.ref013","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12987-019-0130-0","article-title":"Spinal CSF flow in response to forced thoracic and abdominal respiration.","volume":"16","author":"G Aktas","year":"2019","journal-title":"Fluids Barriers CNS."},{"issue":"1","key":"pone.0244090.ref014","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/2045-8118-10-36","article-title":"Influence of respiration on cerebrospinal fluid movement using magnetic resonance spin labeling.","volume":"10","author":"S Yamada","year":"2013","journal-title":"Fluids Barriers CNS"},{"issue":"6","key":"pone.0244090.ref015","first-page":"1039","article-title":"Lumbar puncture for obtaining cerebrospinal fluid in the rhesus monkey (Macaca mulatta).","volume":"27","author":"OC Snead","year":"1977","journal-title":"Lab Anim Sci"},{"issue":"1","key":"pone.0244090.ref016","first-page":"123","article-title":"Baseline values for adult baboon cerebrospinal fluid","volume":"21","author":"TM Butler","year":"1971","journal-title":"Lab Anim Sci"},{"issue":"1","key":"pone.0244090.ref017","first-page":"107","article-title":"Baseline values of cerebrospinal fluid from the chimpanzee (Pan troglodytes).","volume":"20","author":"SK Derwellis","year":"1970","journal-title":"Lab Anim Care"},{"issue":"2","key":"pone.0244090.ref018","first-page":"269","article-title":"Serum and cerebral spinal fluid chemistry values for the monkey (Macaca mulatta).","volume":"20","author":"CL Turbyfill","year":"1970","journal-title":"Lab Anim Care."},{"issue":"18","key":"pone.0244090.ref019","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/0024-3205(82)90038-8","article-title":"Diurnal rhythms of serotonin in monkey cerebrospinal fluid","volume":"31","author":"PL Taylor","year":"1982","journal-title":"Life Sci"},{"issue":"5","key":"pone.0244090.ref020","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1213\/ANE.0000000000002011","article-title":"Computational and in vitro experimental investigation of intrathecal drug distribution: parametric study of the effect of injection volume, cerebrospinal fluid pulsatility, and drug uptake.","volume":"124","author":"KM Tangen","year":"2017","journal-title":"Anesthesia & Analgesia."},{"issue":"2","key":"pone.0244090.ref021","doi-asserted-by":"crossref","first-page":"e0212239","DOI":"10.1371\/journal.pone.0212239","article-title":"Characterization of intrathecal cerebrospinal fluid geometry and dynamics in cynomolgus monkeys (macaca fascicularis) by magnetic resonance imaging.(Research Article)(Report).","volume":"14","author":"M Khani","year":"2019","journal-title":"PLoS ONE."},{"issue":"3","key":"pone.0244090.ref022","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuroimage.2006.01.015","article-title":"User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability.","volume":"31","author":"PA Yushkevich","year":"2006","journal-title":"Neuroimage"},{"key":"pone.0244090.ref023","article-title":"MR Measurement of Cerebrospinal Fluid Velocity Wave Speed in the Spinal Canal","author":"W Kalata","year":"2009","journal-title":"IEEE transactions on bio-medical engineering"},{"issue":"12","key":"pone.0244090.ref024","doi-asserted-by":"crossref","first-page":"e52284","DOI":"10.1371\/journal.pone.0052284","article-title":"Comparison of 4D phase-contrast MRI flow measurements to computational fluid dynamics simulations of cerebrospinal fluid motion in the cervical spine.","volume":"7","author":"TI Yiallourou","year":"2012","journal-title":"PLoS One."},{"issue":"10","key":"pone.0244090.ref025","doi-asserted-by":"crossref","first-page":"e75335","DOI":"10.1371\/journal.pone.0075335","article-title":"Hydrodynamic and longitudinal impedance analysis of cerebrospinal fluid dynamics at the craniovertebral junction in type I Chiari malformation.","volume":"8","author":"BA Martin","year":"2013","journal-title":"PLoS One."},{"issue":"4","key":"pone.0244090.ref026","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1093\/ilar.48.4.396","article-title":"Monkey models of recovery of voluntary hand movement after spinal cord and dorsal root injury.","volume":"48","author":"C Darian-Smith","year":"2007","journal-title":"ILAR J"},{"issue":"Jun","key":"pone.0244090.ref027","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1017\/S0022112081001894","article-title":"Streaked Flow around an Oscillating Circular-Cylinder","volume":"107","author":"H Honji","year":"1981","journal-title":"J Fluid Mech"},{"issue":"Sep","key":"pone.0244090.ref028","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1017\/S0022112084001907","article-title":"On the Stability of the Unsteady Boundary-Layer on a Cylinder Oscillating Transversely in a Viscous-Fluid","volume":"146","author":"P Hall","year":"1984","journal-title":"J Fluid Mech"},{"issue":"3","key":"pone.0244090.ref029","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/clinids\/9.3.595","article-title":"Treatment of infections of cerebrospinal fluid shunts","volume":"9","author":"RL McLaurin","year":"1987","journal-title":"Rev Infect Dis"},{"issue":"1","key":"pone.0244090.ref030","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0006-8993(85)91383-6","article-title":"Evidence for a Paravascular Fluid Circulation in the Mammalian Central Nervous-System, Provided by the Rapid Distribution of Tracer Protein Throughout the Brain from the Subarachnoid Space","volume":"326","author":"ML Rennels","year":"1985","journal-title":"Brain Res"},{"issue":"4","key":"pone.0244090.ref031","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3171\/jns.1997.86.4.0686","article-title":"Arterial pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in the sheep spinal cord","volume":"86","author":"MA Stoodley","year":"1997","journal-title":"Journal of Neurosurgery"},{"issue":"1","key":"pone.0244090.ref032","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ymthe.2006.02.018","article-title":"The \"perivascular pump\" driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain.","volume":"14","author":"P Hadaczek","year":"2006","journal-title":"Mol Ther"},{"issue":"1","key":"pone.0244090.ref033","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12987-017-0085-y","article-title":"A 3D subject-specific model of the spinal subarachnoid space with anatomically realistic ventral and dorsal spinal cord nerve rootlets.","volume":"14","author":"LR Sass","year":"2017","journal-title":"Fluids Barriers CNS"},{"key":"pone.0244090.ref034","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1017\/S0022112076000177","article-title":"Experiments on Transition to Turbulence in an Oscillatory Pipe-Flow","volume":"75","author":"M Hino","year":"1976","journal-title":"J Fluid Mech"},{"issue":"9","key":"pone.0244090.ref035","doi-asserted-by":"crossref","DOI":"10.1002\/cnm.2853","article-title":"Direct numerical simulation of transitional hydrodynamics of the cerebrospinal fluid in Chiari I malformation: The role of cranio-vertebral junction.","volume":"33","author":"K Jain","year":"2017","journal-title":"International Journal for Numerical Methods in Biomedical Engineering"},{"issue":"1","key":"pone.0244090.ref036","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1115\/1.1336144","article-title":"Hydrodynamic modeling of cerebrospinal fluid motion within the spinal cavity","volume":"123","author":"F Loth","year":"2001","journal-title":"J Biomech Eng"},{"issue":"8","key":"pone.0244090.ref037","doi-asserted-by":"crossref","first-page":"081012","DOI":"10.1115\/1.4040401","article-title":"Anthropomorphic Model of Intrathecal Cerebrospinal Fluid Dynamics Within the Spinal Subarachnoid Space: Spinal Cord Nerve Roots Increase Steady-Streaming","volume":"140","author":"M Khani","year":"2018","journal-title":"Journal of Biomechanical Engineering"},{"issue":"8","key":"pone.0244090.ref038","doi-asserted-by":"crossref","DOI":"10.1115\/1.4036608","article-title":"Nonuniform Moving Boundary Method for Computational Fluid Dynamics Simulation of Intrathecal Cerebrospinal Flow Distribution in a Cynomolgus Monkey","volume":"139","author":"M Khani","year":"2017","journal-title":"J Biomech Eng"},{"issue":"8","key":"pone.0244090.ref039","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1136\/jnnp.2003.023168","article-title":"Features of the Sinushunt (R) and its influence on the cerebrospinal fluid system.","volume":"75","author":"A Eklund","year":"2004","journal-title":"J Neurol Neurosur Ps"},{"issue":"7","key":"pone.0244090.ref040","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/ner.12693","article-title":"Intrathecal Therapeutics: Device Design, Access Methods, and Complication Mitigation.","volume":"21","author":"SJ Nagel","year":"2018","journal-title":"Neuromodulation"},{"issue":"2","key":"pone.0244090.ref041","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/jmri.25591","article-title":"Quantifying the influence of respiration and cardiac pulsations on cerebrospinal fluid dynamics using real-time phase-contrast MRI","volume":"46","author":"S Yildiz","year":"2017","journal-title":"J Magn Reson Imaging"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T14:38:39Z","timestamp":1609339119000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244090"}},"subtitle":[],"editor":[{"given":"Quan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,30]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0244090","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.27.222646","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,30]]}}}